Drug-induced dreams during intravenous sedation vary by pharmacological agent and influence patient experiences, yet the role of preoperative positive suggestions in modulating these dreams is unclear. This study aimed to investigate the impact of preoperative positive suggestions on drug-induced dream recall (DIDR) frequency, dream content, and subjective perceptions during sedation with propofol or ketamine. This prospective, randomized, controlled, double-blinded trial with a 2 × 2 factorial design was conducted at a single tertiary university hospital in South Korea from September 2024 to January 2025. A total of 188 adults (American Society of Anesthesiologists [ASA] physical status I-III), aged 20 to 65, undergoing elective upper extremity surgery with sedation via brachial plexus block were enrolled, excluding those with cognitive or psychiatric disorders or recent sedative use. Patients were randomly assigned to 4 groups: propofol with suggestions (P-S; n = 47), propofol without suggestions (P-NS; n = 47), ketamine with suggestions (K-S; n = 47), and ketamine without suggestions (K-NS; n = 47). The suggestion intervention involved providing 8 pleasant dream scenarios preoperatively. The primary outcome was DIDR frequency (binary: yes/no). Secondary outcomes included dream content, subjective dream perceptions, and predictors of DIDR. In the intention-to-treat analysis (n = 188), DIDR frequencies were 21.3% (P-NS), 25.5% (P-S), 36.2% (K-NS), and 44.7% (K-S), with a significant difference between K-S and P-NS ( P = .010). Factorial analysis showed a significant main effect of drug type (ketamine versus propofol: odds ratio [OR] = 2.14, 95% confidence interval [CI], 1.23-3.72; P = .007), but no main effect of suggestions (OR = 1.16, 95% CI, 0.67-2.01; P =.598) or interaction ( P = .818). DIDR frequencies were 23.4% (propofol groups: P-NS and P-S) vs 40.4% (ketamine groups: K-NS and K-S) ( P = .002), and 35.1% (suggestion groups: P-S and K-S) vs 28.7% (no-suggestion groups: P-NS and K-NS) ( P = .308). A significant difference was noted between K-S and P-NS (44.7% vs 21.3%; P = .010). Ketamine increased emotional intensity ( P = .0071 versus P-NS; P = .003 vs P-S) and dream strangeness ( P = .0071 versus P-NS; P = .0071 versus P-S) versus propofol. Suggestions enhanced dream pleasantness in both drug groups ( P = .002 versus P-NS; P = .001 versus K-NS; P = .0071 versus K-S). Preoperative suggestions did not increase DIDR frequency or alter dream content but improved dream pleasantness, indicating potential psychological benefits during sedation.

Trauma is a major public health concern that often leads to long-term psychological distress and chronic pain. Benzodiazepines (BZDs) are sometimes prescribed for anxiety, insomnia, or acute stress-related symptoms, but long-term use is associated with dependence and adverse outcomes. The extent to which BZDs are initiated after trauma, and their implications for long-term health, remain poorly understood. This study aimed to assess the association between trauma exposure and initiation of high-potency BZDs, identify risk factors within the trauma cohort and examine the association between new BZD use and long-term mortality. We conducted a population-based cohort study using data from a regional trauma registry linked to Swedish national health registers. New initiation of BZD prescriptions was defined as filling at least one prescription within 6 months after trauma. Multivariable logistic regression was used to assess associations between trauma exposure and BZD initiation and to identify risk factors within the trauma cohort. Cox proportional hazards regression evaluated the association between new BZD use and 6-18-month mortality. The study included 12,206 BZD-naive trauma patients and 66,801 matched controls. Trauma exposure was independently associated with new high-potency BZD use. Within the trauma cohort, risk factors included older age, psychiatric comorbidity, substance abuse, pre-traumatic opioid or sedative-hypnotic drug use, penetrating trauma, and higher injury severity. New BZD use was associated with markedly elevated 6-18-month mortality (adjusted HR 2.9, 95% CI 2.0-4.2, p < 0.001), a finding that reflects the complex clinical and psychosocial vulnerability of this group. Trauma exposure independently predicted initiation of high-potency BZDs among previously BZD-naive patients. Psychiatric comorbidity, substance use, and greater injury severity were important risk factors. The association between new BZD use and increased long-term mortality underscores the need for cautious prescribing and structured follow-up after trauma. This study examines initiation of high-potency benzodiazepines among previously naive survivors of severe trauma using linked registry data. It shows that trauma exposure is strongly associated with new benzodiazepine use, particularly in older, comorbid, and vulnerable patients. Initiation is also associated with higher subsequent mortality, likely reflecting underlying clinical and psychosocial risk rather than a causal drug effect.

Extraction surgery often induces anxiety and fear in patients with dental phobia. Traditional sedation protocols have limitations such as insufficient depth of sedation and incomplete analgesia. Remimazolam tosilate (RT) and remifentanil hydrochloride (RH), as novel sedative-analgesic agents, have pharmacokinetic advantages of rapid onset, short duration of action, and no accumulation, and may be more suitable for the management of phobia during extraction surgery. This study aims to investigate the efficacy of RT combined with RH in alleviating phobia in patients undergoing extraction and its clinical safety. A total of 262 patients undergoing complex extraction surgery were assigned to the experimental group (EG, n = 131) and the control group (CG, n = 131). The EG was administered an individualized regimen of RT + RH, while the CG received propofol intravenous sedation. The level of fear was assessed using the dental anxiety scale (DAS, with a score range of 11-55, ≥31 indicates severe anxiety). Sedation depth (Ramsay score), visual analogue scale (VAS), vital signs, and adverse events were monitored concurrently. Patient satisfaction was also recorded (on a scale of 0-10, with ≥7 indicating satisfaction). The DAS score of the EG was significantly lower than that of the CG after surgery (12.3 ± 3.2 vs 22.5 ± 4.7, P < 0.05). The VAS pain score (1.23 ± 0.45 vs 3.48 ± 1.21, P < 0.05) and pharyngeal reflex score (1.8 ± 0.6 vs 3.5 ± 0.9, P < 0.05) of the EG were also significantly better than those of the CG. The patient satisfaction score of the EG (9.12 ± 0.89) was significantly higher than that of the CG (7.23 ± 1.45) (P < 0.05). Moreover, the postoperative systolic blood pressure (122.3 ± 10.5 vs 135.6 ± 12.3mmHg), heart rate (72.5 ± 8.3 vs 85.6 ± 9.7 beats/min), and other vital signs of the EG were more stable, and the incidence of angina (0.76% vs 2.29%) and hypertension (1.53% vs 3.82%) were significantly reduced (P < 0.05). The combination of RT and RH can effectively alleviate dental phobia in patients undergoing extraction, enhance the effects of sedation and analgesia as well as patient comfort, and has good safety, which is worthy of clinical application and promotion.

Sedative-hypnotics, including benzodiazepines (BZDs) and non-benzodiazepine hypnotics (Z-drugs), are widely prescribed for insomnia and anxiety, particularly in older adults. Their long-term cognitive safety and potential association with Alzheimer's disease (AD) remain uncertain. We examined whether use of BZDs and Z-drugs is associated with incident AD and assessed variation by drug class, pharmacokinetics, and methodological factors. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to 16 August 2025 without language restrictions. Reference lists of eligible articles and reviews were screened. We included observational cohort and nested case-control studies enrolling adults without dementia at baseline that compared BZD or Z-drug users with non-users and reported incident AD diagnosed using validated clinical or administrative criteria (e.g., ICD-9/10, NINCDS-ADRDA, or NIA-AA). We excluded reviews, case reports, conference abstracts, studies with overlapping populations, and studies without extractable effect estimates. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-E. Random-effects meta-analyses were performed separately for odds ratios (ORs) and hazard ratios (HRs). Heterogeneity was quantified with I2. Publication bias was evaluated with funnel plots and Egger test when applicable. Subgroup and meta-regression analyses assessed clinical and methodological modifiers. Certainty of evidence was rated using GRADE. The protocol was prospectively registered (PROSPERO CRD420251141623). Thirteen studies (N = 721,354 subjects) were included. Overall sedative-hypnotic use was associated with higher odds of AD (OR 1.29; 95% CI, 1.10-1.53; I2 = 86.5%). Estimates restricted to HRs were attenuated and not statistically significant (HR 1.17; 95% CI, 0.87-1.58; I2 = 73.1%). In subgroup analyses, BZDs overall (OR 1.21; 95% CI 1.07-1.36), Z-drugs (OR 1.14; 95% CI 1.10-1.18; I2 = 0%), and short-acting agents (OR 1.19; 95% CI 1.04-1.36) were associated with higher odds of AD, whereas broad-acting BZDs were not (OR 1.01; 95% CI 0.98-1.05). Long-acting agents showed a borderline estimate (OR 1.44; 95% CI 0.99-2.09). Age-stratified analyses showed higher odds in individuals aged <75 years (OR 1.36; 95% CI 1.24-1.49), but not in those aged ≥75 years (OR 1.14; 95% CI 0.61-2.11). Estimates were also higher in studies using ICD-based definitions (OR 1.47; 95% CI 1.16-1.86) than in those using clinical criteria (OR 1.13; 95% CI 0.84-1.52). Meta-regression identified drug class and publication year as significant moderators. Risk of bias was rated moderate to serious in several studies, mainly due to residual confounding and exposure misclassification. Certainty of evidence ranged from very low to moderate. Use of BZDs and Z-drugs was associated with increased odds of AD, with variation across drug classes and pharmacokinetic profiles. Short-acting agents, BZDs overall, and Z-drugs were associated with higher risk, whereas broad-acting BZDs were not; this finding should be interpreted with caution given subgroup heterogeneity and limited statistical power. Residual confounding and reverse causation limit causal inference. These results support careful prescribing and the need for prospective studies with detailed characterization of exposure, dose, duration, and clinical indication to clarify whether observed associations reflect drug-related effects or underlying disease processes. PROSPERO protocol number: CRD420251141623.

This study compared the sedative effects of intravenous etomidate/fentanyl/midazolam versus propofol/fentanyl/midazolam combination, with a primary focus on behavioral outcomes assessed by the Houpt scale and hemodynamic safety, for dental treatment of uncooperative children between 3 and 10 years. This patient- and assessor-blinded, crossover clinical trial was conducted on 40 children (27 females, 13 males; mean age, 4.67 ± 1.46 years; mean weight, 15.93 ± 4.2kg) with negative and very negative behavior, as assessed by the Frankl scale. The children were randomly assigned to 2 groups (n = 20). Group 1 received etomidate (0.2mg/kg), fentanyl (1µg/kg), and midazolam (0.2mg/kg) combination in the first treatment session, and propofol (1mg/kg), fentanyl (1µg/kg), and midazolam (0.2mg/kg) in the second treatment session. This order was reversed in group 2. Hemodynamic indices, including the heart rate (HR) and arterial oxygen saturation (SPO2), were monitored during the procedure, and the behavior of children was recorded using the Houpt behavioral rating scale. Data were analyzed using the Mann-Whitney and t tests (α = 0.05). The hemodynamic indices were within the safe range, with no significant difference between the two groups (P > 0.05). At the time of injection, a statistically significant but clinically modest difference in SPO2 was observed favoring the etomidate group (99.75% vs. 98.85%, P = 0.003); however, mean SPO2 remained above 97% in both groups throughout all procedures. The mean HR showed greater stability with less fluctuation from baseline in the etomidate group compared to propofol (e.g., smaller magnitude of change at injection in the second session, P < 0.005 overall for key time points). The two groups were similar regarding the Houpt scale, except during recovery, where the etomidate group had a significantly higher behavior score (7.45 vs. 6.60, P = 0.007). Both combinations are highly effective and safe for the intravenous sedation of uncooperative children, providing comparable intra-procedural sedation. However, the etomidate/fentanyl/midazolam combination demonstrated specific advantages regarding intra-procedural heart rate stability and more favorable behavioral scores during the recovery period.Trial registration IRCT20230515058193N1, registeredretrospectively on 22 November 2024 in the Iranian Registry of Clinical Trials (https://www.irct.ir/trial/77589).

Introduction Adverse outcomes, including hospitalization, associated with psychoactive substance use among children and adolescents, remain an important public health issue. This study aimed to assess psychoactive substance-related hospital admissions among minors in France. Methods A national cohort study was conducted using data from the French Hospital Discharge Database. Hospitalizations of individuals aged 11–17 years between 2016 and 2022 were extracted using the International Classification of Diseases 10th Revision (ICD-10) codes (F11-F19 except F17; T40–T43). A descriptive analysis was performed, followed by a gender-specific analysis. Results During the study, 9520 psychoactive substance use-related hospital stays were recorded for 8031 subjects. At the time of entry, the median age was 16 (interquartile range [IQR]: 15–17) years; 52.6% were male. Hospitalizations were primarily associated with cannabis intoxication (44.2%), misuse of benzodiazepines as well as other sedative drugs (28.8%), and multidrug use (11.6%). Overall hospitalization decreased between 2016 and 2022 (incidence rate ratio [IRR] = 0.98; 95% CI, 0.97–1.00; P = 0.019), particularly among males (IRR = 0.97; 95% confidence interval [CI], 0.93–1.00; P = 0.043). Cannabis-related admissions were more frequent in males (55.5% versus 31.6%) whereas psychotropic medication misuse was more commonly reported in females (42.4% versus 16.6%; P <0.001). Discussion Despite an overall decline in psychoactive substance-related hospital stays, the proportion of females increased markedly over the study period. A strong gender contrast was observed in the main substances involved, supporting the need for tailored prevention strategies. Conclusion Raising awareness among young people and their families about the risks of non-medical substance use and psychotropic medications is essential to anticipate and prevent related harms.

Abrupt cessation of alcohol consumption following hospital admission can induce alcohol withdrawal syndrome. This syndrome is challenging to manage and is associated with considerable morbidity and mortality. Current management of alcohol withdrawal syndrome in Australia is generally titrated benzodiazepine administration. In some regions, phenobarbital is preferred but evidence to support its superiority is weak. We will conduct a single-center, three-arm, open-label, parallel-group, randomized clinical trial. Our primary objective is to determine the feasibility of embedding a randomized clinical trial within an electronic medical record to compare phenobarbital to single-agent benzodiazepine for patients with alcohol withdrawal. We will screen and randomize 45 patients using the Epic electronic medical record system. Patients will receive either low- or standard-dose intravenous phenobarbital (4 or 8mg per kilogram), or usual care (benzodiazepine regimen). The primary outcomes to assess feasibility are usability, screening rates, enrollment rates, and compliance. Secondary outcomes are exploratory and include alcohol withdrawal scale scores, dose of benzodiazepine administered, health utilization, adjuvant drug treatments, and patient outcomes. There are limited high quality data evaluating the use of phenobarbital administration for alcohol withdrawal syndrome. Additionally, there is limited data evaluating the embedding of screening, randomization, and administration of a sedative drug within the electronic medical record. Our feasibility trial will establish whether this is possible within our health care system. In this protocol paper we detail how we will embed this trial within the electronic medical record Epic. The study (RMH2024.320 v2 06/01/2025) is registered with Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12625000320459. Registered on 17 April 2025. Trial Sponsor: The Royal Melbourne Hospital.

Exploring the synergistic mechanism of combined hypnotic drugs on sleep in mice based on transcriptomics.

BackgroundPostoperative insomnia is one of the common complaints caused by spinal metastatic cancer surgery. It affects patients’ functional recovery, greatly reduces their quality of life, and adversely impacts disease prognosis. Compared with traditional pharmacological treatments, acupuncture is an alternative therapy for postoperative insomnia. However, standardized, high-quality randomized controlled trials on electroacupuncture for postoperative insomnia in patients with spinal metastasis (SM) are scarce, and there is a lack of clear inclusion criteria for this specific population. Postoperative insomnia in patients with SM has distinct clinical characteristics compared with general cancer-related insomnia, necessitating targeted investigation.ObjectiveThis study aims to evaluate the efficacy and safety of electroacupuncture in the treatment of postoperative insomnia in patients with SM, and to provide high-level clinical evidence for the inclusion of electroacupuncture in the clinical management plan of postoperative insomnia in patients with SM.MethodsThis is a study protocol for a randomized controlled trial. We will randomly assign 196 patients with insomnia after spinal metastatic cancer surgery to the acupuncture group (n=98) or the control group (sham acupuncture group; n=98). All participants will be treated on the first day after surgery and receive 12 sessions in total (30 min per session, 3 sessions per wk for 4 weeks). The primary outcome is the change in Pittsburgh Sleep Quality Index score from baseline to post treatment (wk 4). The secondary outcomes include actigraphy records (sleep efficiency, number of sleep awakenings, total sleep time, sleep latency, and wake after sleep onset), Insomnia Severity Index, Spine Oncology Study Group Outcomes Questionnaire 2.0, and Patient Health Questionnaire-9. All results will adhere to the intention-to-treat principle and will be evaluated at baseline, posttreatment (wk 4), and follow-up (wk 12).ResultsThis study was funded in June 2023 (supported by the Project of Shanghai Municipal Health Commission, National Natural Science Foundation of China, etc). Recruitment will start in mid-2026 and end in December 2027. Data collection will be completed in October 2027, and data analysis is expected to be finished in December 2027. The results of this study are anticipated to be published in the first half of 2028.ConclusionsThis study is designed to rigorously assess the therapeutic value of electroacupuncture for postoperative insomnia in patients with SM. If proven effective, electroacupuncture is expected to become a safe and feasible alternative or complementary therapy for this population, reducing reliance on hypnotic drugs and improving patients’ quality of life and prognosis. The results will fill the gap in current clinical evidence for electroacupuncture in the treatment of spinal metastatic postoperative insomnia and provide a basis for the optimization of clinical treatment strategies.

The configuration of interventional radiology (IR) suites often limits simultaneous access to the patient's airway and anesthesia equipment. This constraint may lead to suboptimal sedation in patients at increased risk of airway obstruction due to patient safety concerns. We conducted a randomized pilot trial to evaluate whether high-flow nasal oxygen (HFNO; F&P Optiflow™) reduces hypoxic events compared with a standard non-rebreather mask in this high-risk population undergoing deep sedation. Patients at increased risk of airway obstruction or hypoxia during deep sedation were randomized to receive 100% oxygen via HFNO at 70L/min (HFNO group) or via non-rebreather mask at 8L/min (standard-of-care [SoC] group). All patients received continuous intravenous propofol to achieve unconsciousness while maintaining spontaneous ventilation. The primary endpoint was total length of desaturation episodes [ToLDE], in minutes, defined as oxygen saturation [SpO2] ≤92%. Secondary outcomes included the number of desaturation episodes, bispectral index (BIS) excursions (defined as episodes of BIS value ≥ 61), postanesthesia care unit (PACU) length of stay, and patient-reported symptoms. A total of 101 patients were analyzed (HFNO group: n = 50; SoC group: n = 51). Mean ToLDE time was 0.34min (median, 0; range 0-6.5min) in the HFNO group and 0.97min (median, 0; range 0-19.8min) in the SoC group (P = 0.158). Desaturation occurred in 14% of HFNO patients vs. 26% of SoC patients (P = 0.212). The median number of BIS excursions was significantly higher in the SoC group (4; range, 0-19) than the HFNO group (2; range, 0-15; P = 0.005). Median PACU stay was shorter in the HFNO group (20min; range, 0-60) vs. in the SOC group (26min; range, 5-60) (P = 0.076). Patient-reported symptoms were less frequent and less severe in the HFNO group (12% vs. 16%). HFNO did not significantly reduce hypoxic events compared with a standard non-rebreather oxygen delivery device in patients at increased risk of airway obstruction during deep intravenous sedation. However, HFNO was associated with improved sedation stability and patient experience, supporting further investigation in larger studies. ClinicalTrials.gov ID: NCT04171037; Date of original registration: November 19, 2019; This study was retrospectively registered. Study principal investigator: Gang Zheng; This manuscript adheres to the applicable Consolidated Standards of Reporting Trials (CONSORT) guidelines.

IntroductionHysteroscopy is a common gynecologic procedure increasingly performed in outpatient settings, yet in Canada cases still occur in operating rooms. As care transitions to ambulatory suites, processes for managing complications remain poorly defined. This educational initiative aimed to design in-situ simulation scenarios to enhance patient safety during outpatient hysteroscopy by strengthening team preparedness and identifying system gaps.MethodsA needs assessment was conducted via literature review and interviews with local staff. Findings informed the creation of 4 simulation scenarios targeting the most common and catastrophic adverse events in the outpatient setting: intravenous sedation overdose, hemorrhage, local anesthetic toxicity, and vasovagal reaction. Physicians and nurses working in the outpatient suite were invited to participate. Surveys assessing self-efficacy components on a 5-point Likert scale were administered pre- and postsimulation.ResultsExisting literature revealed minimal simulation-based training for outpatient hysteroscopy. Twelve participants (8 physicians, 4 nurses), with experience ranging from 6 months to 23 years, engaged in 4 simulation sessions. Across all measured domains, participants reported improved confidence in managing complications.DiscussionSimulation effectively prepares teams for rare, high-acuity events but remains underutilized in ambulatory gynecology. These scenarios can be deployed in simulation centers to enhance crisis resource management or in-situ to uncover latent safety threats and test system readiness. They offer a structured approach to support the safe establishment of outpatient hysteroscopy services and can serve as a continuing quality assurance tool. Implementing standardized, team-based simulation may help close safety gaps as outpatient hysteroscopy becomes the preferred standard of care.

Zopiclone (ZOP) is a sedative-hypnotic drug that is featured commonly in impaired driving, drug-facilitated crimes, accidental overdose, or suicidal intoxications. Further understanding of its blood pharmacokinetics would support its interpretation in forensic toxicology casework. This study characterizes the concentration-time pharmacokinetic profiles of ZOP and its metabolite N-desmethylzopiclone (N-DMZOP) in blood following controlled administration and evaluates the use of metabolite-to-parent ratios in estimating time of last ZOP intake. Sixteen subjects received a single oral dose of either 5 mg or 10 mg Imovane®, and blood samples were collected pre-dosing, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 24, and 48 hours post-dose. A paired plasma sample was also provided at the 2-hour time point. A previously validated LC-MS/MS method was used to quantify ZOP, N-DMZOP, and the degradation product 2-amino-5-chloropyridine (ACP). The aggregate regression model developed from this younger subject population was applied to independently dosed subjects and a separate group of elderly patients to determine the validity of this model in an older cohort of differing pharmacokinetic characteristics. Comparison between the 5 mg and 10 mg dosing groups supported a linear dose-concentration relationship. While the ratio of N-DMZOP/ZOP can be a predictive indicator for time of ZOP intake, inter-individual differences in ZOP disposition may influence such predictions. Furthermore, age-related pharmacokinetic changes may contribute to a general underestimation of predicted time with the current model, but a larger sample size of a broader demographic spectrum and dosing regimen would help improve the general applicability of this ratio-based modeling. Finally, we show that the mean blood-to-plasma ratio for ZOP and N-DMZOP were 0.79 and 0.92, respectively, suggesting a preferential partitioning of ZOP into the plasma fraction, which would be a useful reference when interpreting plasma concentrations from clinical studies against the more routinely sampled whole blood concentrations found in forensic toxicological casework.

Post-operative pain after breast augmentation remains unpredictable, and regional anesthesia alone is seldom described. We evaluated an opioid-free protocol combining pectoral nerves (PECS I-II) and parasternal blocks with intravenous sedation. Between January 2020 and December 2024, 627 women (mean age 35y) underwent bilateral primary augmentation under ultrasound-guided fascial-plane blocks plus sedation. VAS pain scores were recorded at predefined intervals up to 72h. Descriptive statistics, cubic modelling of pain trajectories and Kruskal-Wallis tests compared implant planes; cumulative pain was expressed as the 0-72h area under the curve (AUC). Mean VAS was < 2 in all groups by 72h. Pain peaked at 16h, highest with dual-plane placement (mean 7.0) and lower with submuscular and pre-pectoral placements (both ≈ 5.5; p < 0.001). Inter-group differences persisted to 48h but disappeared by 72h (p = 0.115). AUC confirmed the greatest pain burden for dual-plane (292 VAS·h) versus submuscular (238) and pre-pectoral (200). Implant volume showed only a weak overall correlation with pain (ρ = 0.20) and none within individual planes. No patient required rescue opioids; most resumed normal activities within four days, and no major complications occurred. Ultrasound-guided PECS I-II and parasternal blocks with sedation provide safe, effective, opioid-free analgesia for aesthetic breast augmentation. Early pain is determined mainly by the implant plane, not by implant size, and should be considered in surgical planning and postoperative care. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intravenous (IV) sedation is an effective method of alleviating patient anxiety and pain, thereby improving cooperation during dental procedures. In South Korea, most drugs used for IV sedation are classified as psychotropic substances, which require strict management throughout the processes of administration, storage, and disposal. In 2018, all medical institutions in Korea were mandated to report on the manufacture, import, use, administration, and disposal of narcotic and psychotropic drugs to the Narcotics Information Management System (NIMS). Thus, in this study, we aimed to analyze the current status and trends of narcotic and psychotropic drug use in IV sedation performed at domestic dental clinics and hospitals by year, region, sex, and age using the aforementioned big data. Data on narcotic and psychotropic drug use reported nationwide by dental clinics and hospitals between January 2020 and December 2024 were collected. The drugs analyzed included midazolam, propofol, ketamine, and remimazolam (used for intravenous sedation), as well as fentanyl, remifentanil, and pethidine (used as analgesic adjuncts). Annual trends, regional distributions, and usage ratios by age and sex were analyzed for these medications. During the analysis period, the use of intravenous sedatives in domestic dental practice showed a continuous annual increase. As of 2024, midazolam account for the largest share, at approximately 76.5% of the total sedative use, followed by propofol (10.6%), ketamine (9.9%), and remimazolam (2.8%). Notably, ketamine showed the most rapid growth, with its annual usage increasing by approximately 152% in 2023 compared to the previous year. According to the type of medical institution, the volume of sedatives used in dental clinics account for 90.8% of the sedatives in 2024, indicating a higher growth rate in dental clinics than in dental hospitals. The average annual growth rate of sedative use is high among adults. Regionally, usage tends to become increasingly concentrated in the Seoul Metropolitan Area (Seoul and Gyeonggi). The use of IV sedation in Korean dentistry is consistently increasing. Safe IV sedation methods, primarily involving midazolam, are being widely implemented for adults in dental clinic settings.

Inhaled sedation versus intravenous sedation in ARDS: A systematic review and meta-analysis.

Optimal respiratory management under deep sedation remains a most concerning safety challenge for pediatric dental treatment due to its shared oral cavity. High-flow nasal oxygenation has been found to be advantageous in certain short-duration pediatric procedures and examinations. Our study aimed to further explore its clinical feasibility in preschool-aged pediatric dental treatment under deep intravenous sedation of prolonged and more complex procedures. This study involved twenty pediatric patients scheduled for elective dental treatment with anticipated operation time of 60-120min under deep sedation. Sedative/anesthetic agents, oxygenation management and perioperative monitoring were performed by qualified anesthesiologists. IV insertion was conducted after the child was calmed with intranasal dexmedetomidine or under general anesthesia with mask inhalation of sevoflurane. During dental treatment, oxygen administration was provided with the HFNO device with a 2.0L/kg/min gas flow rate and an FiO2 of 1.0. Depth of sedation was maintained by propofol with a target-controlled infusion system. Perioperative pulse oximetry, respiratory status, remedial maneuvers and adverse effects were recorded in detail. All included children successfully completed dental treatment under deep sedation. The average operation time was 74min. None of the participants experienced any desaturation and no related complications were reported in our observation and 24h follow-up. Based on our initial experience, HFNO could provide ideal oxygenation in preschool-aged pediatric dental treatment under deep sedation without clinically observed complications and adverse events. Whereas the provider qualification, strict training of HFNO device, proper use and close monitoring must be emphasized. The study was registered at ClinicalTrials.gov (No. NCT05762692) and first posted on 10/03/2023.

To evaluate the effectiveness and safety of interlaminar versus transforaminal endoscopic lumbar discectomy (IELD versus TELD) in treating L4/5 highly migrated lumbar disc herniation (HM-LDH), and to analyze factors influencing surgical approach selection. From January 2022 to June 2024, patients with L4/5 HM-LDH treated with IELD or TELD were retrospectively included. Patients were divided into two groups based on the approach used: IELD (under general anesthesia) and TELD (under local anesthesia with intravenous sedation). Baseline data, perioperative data, radiological data, patient-reported outcomes (PROs) including the visual analogue scale (VAS), Oswestry Disability Index (ODI), and modified MacNab criteria were recorded. All data were compared and analyzed by independent t-tests and χ² tests. There were 50 patients in the IELD group and 80 patients in the TELD group respectively. The baseline data between the two groups did not show significant difference. The IELD group had relatively wider interlaminar window and thinner intervertebral foramen at L4/5, while there is no significant difference in the height of the intervertebral foramen between the two groups. No significant differences were found in intraoperative blood loss and postoperative length of stay. However, IELD had a shorter operation time (86.6 ± 12.6min vs.99.4 ± 27.4min, P < 0.001) and less fluoroscopy times (4.3 ± 1.1 vs. 11.6 ± 1.9, P < 0.001) compared to TELD. Both groups achieved a significant improvement in VAS and ODI after surgery. Satisfaction rates were 92.0% for IELD and 91.3% for TELD (P = 0.816) according to the modified MacNab criteria. As compared to preoperative measurements, both groups showed a significant reduction in the anteroposterior diameter of the intervertebral disc (APDID) and a significant increase in dural sac cross-sectional area (DSCA) at 12 months postoperatively. No significant differences in complications were observed between the two groups. Regarding residual symptoms, there were more patients in the TELD group who reported residual back pain (VAS ≥ 2) during the follow-up periods (33.8% vs. 16.0%, P = 0.026). Both IELD and TELD can achieve satisfactory clinical and radiological outcomes in treating L4/5 HM-LDH. IELD has advantages of shorter operation time, less fluoroscopy times and fewer residual back pain compared with TELD. Selection of surgical approach for L4/5 HM-LDH depends on anatomical structure, migration characteristics, and the operative skills of the surgeon.

Background/Objectives: Preoperative anxiety is common in adult patients undergoing oral and dentoalveolar surgical procedures under local anesthesia and may impair cooperation, physiological stability, and overall treatment experience. While intravenous sedation and general anesthesia provide effective anxiolysis, they increase anesthetic exposure and recovery demands. Targeted preoperative anxiolysis offers a less invasive strategy to reduce anxiety while preserving responsiveness. However, approaches vary and standardized protocols are lacking. This systematic review evaluated the efficacy and safety of preoperative anxiolytic interventions-including both pharmacological and non-pharmacological strategies-in adult patients undergoing oral surgical procedures under local anesthesia without general anesthesia or deep sedation. Methods: The review adhered to the PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420261281592). Randomized and quasi-randomized controlled trials published between 2016 and 2026 were identified through structured searches of PubMed/MEDLINE, ScienceDirect, and Springer Nature Link. Eligible studies included adult patients undergoing oral surgery under local anesthesia and evaluated preoperative anxiolysis using validated instruments such as the Dental Anxiety Scale (DAS), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale for Anxiety (VAS-A). Risk of bias was assessed using the Cochrane RoB 2 tool. Owing to methodological heterogeneity, results were synthesized narratively. Results: Eight trials (n = 617) met the inclusion criteria. Interventions included oral benzodiazepines, melatonin, pregabalin, herbal agents, nitrous oxide, and auriculotherapy. Benzodiazepines consistently reduced anxiety scores (p < 0.05) without significant interagent differences. Pregabalin at a dose of 150 mg significantly lowered STAI-S and VAS-A scores (p < 0.001). Passiflora incarnata was comparable to midazolam and superior to placebo, whereas Erythrina mulungu showed no effect. Melatonin results were inconsistent. Hemodynamics remained stable, and adverse events were mild. Conclusions: Preoperative anxiolysis under local anesthesia effectively reduces anticipatory anxiety in oral surgery, with benzodiazepines demonstrating the most consistent efficacy. Further standardized trials are warranted.

Environmental sustainability is a major priority in modern anaesthesia [1]. Currently, total intravenous anaesthesia (TIVA) is often considered more environmentally friendly than volatile inhalational anaesthesia because it has reduced greenhouse gas emissions. However, this view ignores the potential water pollution caused by intravenous drugs. Propofol, used widely in TIVA, is a phenol derivative that is detected frequently in hospital wastewater due to significant clinical wastage [2]. As a lipophilic compound, propofol may accumulate in aquatic organisms, posing a risk to the ecosystem. The introduction of remimazolam, an ultra-short-acting benzodiazepine, offers a potential alternative for TIVA. Unlike propofol, remimazolam is hydrolysed rapidly by tissue esterases into a carboxylic acid metabolite (CNS 7054) [3]. The environmental impact of this metabolite is not well understood. The aim of this study was to utilise in-silico quantitative structure–activity relationship modelling to compare the predicted aquatic toxicity of propofol and the remimazolam metabolite, providing a more complete ecological assessment. Aquatic toxicity was evaluated using the Ecological Structure Activity Relationships Class Program (Version 2.2; United States Environmental Protection Agency) [4]. This in-silico methodology aligns with ‘replacement, reduction and refinement’ principles, offering an ethical alternative to in-vivo animal testing for risk assessment [5]. We retrieved the chemical structures of propofol and the remimazolam metabolite (CNS 7054) from the PubChem database and converted them into Simplified Molecular Input Line Entry System codes. The model predicts toxicity based on structure-specific regression equations derived from measured data. We analysed the octanol–water partition coefficient (LogKow) to estimate bioaccumulation potential and calculated standard acute toxicity endpoints (LC50 and EC50) for fish, daphnids and green algae. Propofol is characterised by a high octanol–water partition coefficient (LogKow 3.79), classifying it as a lipophilic substance with significant bioaccumulation potential. In contrast, CNS 7054 exhibits a low LogKow of 1.25, indicating high water solubility and minimal risk of bioaccumulation. In terms of acute toxicity, propofol was predicted to be toxic to aquatic organisms, with 96-h LC50 values of 4.6 mg.l-1 for fish and 48-h LC50 values of 0.85 mg.l-1 for daphnids. Conversely, CNS 7054 was predicted to be practically non-toxic across all trophic levels, with estimated lethal concentrations exceeding 100 mg.l-1 (Table 1). While propofol is favoured for its lack of greenhouse gas emissions, our data suggest it poses a persistent threat to aquatic ecosystems due to its lipophilic nature and potential for bioaccumulation. In recent years, remimazolam has emerged as a valuable drug for procedural sedation and general anaesthesia [6, 7]. As its clinical use expands, its environmental profile becomes increasingly relevant. Remimazolam appears to exemplify the principles of ‘benign-by-design’ pharmaceuticals. Its rapid hydrolysis into a highly polar, hydrophilic metabolite ensures that the excreted compound does not accumulate in aquatic organisms and is virtually non-toxic. We acknowledge several limitations in this study. First, the results are based on in-silico predictions rather than in-vivo biological assays. However, the quantitative structure–activity relationship is a validated tool for initial risk screening [5]. Second, we focused solely on the excretion phase. A complete life-cycle assessment is necessary to determine the total carbon footprint. Crucially, such future comparisons must ensure clinical equipotency. Since remimazolam often exhibits higher bispectral index values than propofol at equivalent sedation levels [7], strictly adhering to traditional bispectral index targets may lead to overdosing and an unfair inflation of its environmental impact. We recommend that future comparative studies standardise anaesthetic depth using multiparametric monitoring to ensure a fair ecological comparison. In conclusion, while propofol remains a cornerstone of TIVA, its environmental footprint extends into the water cycle. Remimazolam offers a promising alternative with a significantly more favourable aquatic safety profile. Future ‘green anaesthesia’ strategies should adopt a holistic view, balancing carbon mitigation with the protection of water resources. No external funding or competing interests declared.

Due to its large gyrencephalic brain, the pig is increasingly used for neuroscience research, especially for the preclinical testing of novel neuroprostheses. However, our understanding of the pig's motor system remains limited compared with the common species used for neuroscience research. Here, we aimed to characterize the forelimb and hindlimb representation of the pig motor cortex using intracortical microstimulation (ICMS). Three domestic pigs (Sus scrofa) were placed in a modified stereotactic frame and maintained under intravenous propofol sedation. We mapped the motor cortex using ICMS, applied at varying cortical coordinates and depths. For each site, we recorded the electrode depth eliciting the maximal limb response and determined the motor threshold. Responses were assessed visually and via electromyographic recordings. ICMS uncovered a large forelimb representation, with stereotypical contralateral responses. Conversely, the hindlimb representation was smaller and located within the interhemispheric fissure. The mean threshold of the five most responsive forelimb sites was 75 ± 25 μA, compared with 280 ± 45 μA for hindlimb sites (P < 0.01). A summation of stimulations in the hindlimb representation of the motor cortex unilaterally triggered bilateral alternating hindlimb movements. These results suggest that while the porcine cortex can directly command forelimb movements via the corticospinal pathway, cortical control of hindlimb likely relies on polysynaptic pathways through the brainstem, such as the corticoreticulospinal pathway.NEW & NOTEWORTHY We identified a limited hindlimb representation on the medial surface of the pig motor cortex that, when repeatedly stimulated, produced bilateral alternating hindlimb movements. This suggests that the cortical control of hindlimb likely relies on polysynaptic pathways through the brainstem, such as the corticoreticulospinal pathway.