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Background: In clinical practice, family medication history is not routinely assessed as part of a patient's family health history (FHH). The information is self-reported and can depend on the individual's subjective perception. To illustrate how pharmacogenetic (PGx) testing results could be used to validate self-reported family medication history on drug-related problems (DRP), as well as to inform medication-related decisions, we herein present a case involving ten members of the same family., Case Presentation: Prior to a planned surgery, a preemptive PGx panel test was performed for a nine-year-old girl due to self-reported family medication history. The PGx panel test was also performed for her three siblings, parents, and grandparents. The focus was directed to the paternal grandmother, as she reported DRP from the hypnotic agent propofol, and to the maternal grandmother, as she described DRP after the administration of codeine and tramadol. A commercial PGx panel test of 100 variations in 30 different genes was conducted and analyzed focusing on genetic variants in cytochrome P450 enzyme 2B6 (CYP2B6), and CYP2D6 as they are involved in the biotransformation of propofol and the bioactivation of codeine and tramadol, respectively. The girl was identified as (1) CYP2B6 intermediate metabolizer (IM) with reduced enzyme activity and (2) CYP2D6 poor metabolizer (PM) with no enzyme activity. Regarding the planned surgery, it was recommended (1) to carefully titrate propofol dosage with increased monitoring of potential DRP and (2) to avoid opioids whose activation is mediated by CYP2D6 (e.g. codeine and tramadol). Further PGx testing revealed (1) the paternal grandmother as CYP2B6 normal metabolizer (NM) and (2) the maternal grandmother as CYP2D6 NM., Conclusion: The original trigger for PGx testing was the self-reported, conspicuous family medication history of DRP reported by the grandmothers. However, the girl's genotype predicted phenotypes of CYP2B6 IM and CYP2D6 PM, differed from the grandmothers'. With this exemplary case, we propose that hereditary concerns based on self-reported information on DRP should be verified by a PGx panel test, when the respective drug exhibits a PGx association. Also, the girl's PGx testing results provided important medication recommendations, which were considered perioperatively by the anesthetist suggesting to use PGx testing results preemptively to inform medication-related decisions., Competing Interests: Declarations Ethics approval and consent to participate All ten patients provided written informed consent to use the data for research purposes. The six adult patients were part of the observational study “Pharmacogenetic Testing of Patients with unwanted Adverse Drug Reactions or Therapy Failure”, which was conducted according to the guidelines of the Declaration of Helsinki and approved by the local ethics committee of “Ethikkommission Nordwest- und Zentralschweiz” (2019 − 01452, 31.10.2019). Consent for publication All ten patients provided written informed consent for publishing this case report. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Rationale: Uncertainty remains regarding the risks associated with single-dose use of etomidate. Objectives: To assess the use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. Methods: We assessed patients who received invasive mechanical ventilation (IMV) and were admitted to an ICU in the Premier Healthcare Database between 2008 and 2021. The exposure was receipt of etomidate on the day of IMV initiation, and the main outcome was hospital mortality. Using multivariable regression, we compared patients who received IMV within the first 2 days of hospitalization who received etomidate with propensity score-matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. Measurements and Main Results: Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first 2 days of hospitalization, we established 22,273 matched pairs administered either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs. 18.7%; absolute risk difference, 2.8%; 95% confidence interval, 2.1%, 3.6%; adjusted odds ratio, 1.28, 95% confidence interval, 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days after etomidate use. Conclusions: Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality than use of ketamine. This finding is independent of subsequent treatment with corticosteroids.

Introduction: Hypoxemia is a common complication of sedation. This meta-analysis aimed to evaluate the efficacy and safety of supraglottic jet oxygenation and ventilation (SJOV) in preventing hypoxemia during sedative procedures., Methods: Randomized controlled trials (RCTs) that compared SJOV with conventional oxygen therapy in sedated patients were searched in five databases (MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure [CNKI], and Google Scholar) from their inception to March 2024. The primary outcome was the proportion of patients who developed hypoxia (SpO 2  < 90%). The secondary outcomes included subclinical respiratory depression (90% ≤ SpO 2  < 95%), severe hypoxemia (SpO 2  < 75%), airway interventions, adverse events, hemodynamics, propofol dosage, and procedure time. The certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Twelve trials (n = 3058) were included in the analysis. The evidence suggests that SJOV results in a large reduction in the risk of hypoxemia (risk ratio [RR], 0.26; 95% confidence interval, 0.19-0.36; low certainty) and subclinical respiratory depression (RR, 0.40; low certainty) compared with the control. SJOV likely resulted in a large reduction in the risk of severe hypoxemia (RR, 0.22; moderate certainty). In addition, it may result in a large reduction in the need for jaw lift (RR, 0.22; low certainty) and mask ventilation (RR, 0.13; low certainty). The risk of sore throat probably increases with SJOV (RR, 1.71; moderate certainty), whereas SJOV may result in little to no difference in nasal bleeding (RR, 1.75; low certainty). Evidence is very uncertain regarding the effect of SJOV on hemodynamics (very low certainty) and procedure time (very low certainty). SJOV probably resulted in little to no difference in sedative doses between the groups (moderate certainty)., Conclusion: According to the GRADE approach, SJOV likely results in a large reduction in the risk of severe hypoxemia but probably increases the risk of sore throat. Compared with the control, evidence suggests that SJOV results in a large reduction in the risk of hypoxemia, subclinical respiratory depression, and the need for airway manipulation, with little to no difference in nasal bleeding. The integration of SJOV into clinical practice may help minimize hypoxemic events in at-risk patients., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: Maintaining haemodynamic stability is crucial but challenging during the induction and maintenance of general anaesthesia (GA) in patients undergoing off-pump coronary artery bypass grafting (OPCABG). Remimazolam tosylate is a novel ultra-short-acting benzodiazepine with minimal cardiovascular depression. Currently, non-inferior studies comparing the haemodynamic changes induced by remimazolam and etomidate are limited. This study aims to assess the efficacy and safety of remimazolam tosylate for the induction and maintenance of GA in patients undergoing OPCABG., Method and Analysis: This two-armed non-inferiority randomised controlled trial will include 88 patients aged 18-75 years who are scheduled for OPCABG. Patients will be randomly assigned in a 1:1 ratio to receive either remimazolam tosylate or etomidate and propofol for anaesthesia induction and maintenance. The primary outcome will be the fluctuation of mean artery pressure during anaesthesia induction. Secondary outcomes will include adverse events, adverse drug reactions, the cumulative dosage of vasoactive drugs, vital signs and bispectral index values at different time points, lengths of postoperative mechanical ventilation and tracheal intubation, lengths of intensive care unit stay and hospital stay and hospital mortality. Analyses will be conducted using both the intention-to-treat approach and the per-protocol approach., Ethics and Dissemination: This study was approved by the Ethics Committee of Zibo Central Hospital (No. 2024001). The trial results will be submitted to an international peer-reviewed journal., Trial Registration Number: ChiCTR.gov.cn: ChiCTR2400079615., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Little is known about the impact of different anesthetic agents used for routine magnetic resonance imaging (MRI) sedation on pulmonary function in children., Objective: To compare the incidence of pulmonary atelectasis after MRI sedation with propofol vs propofol-ketamine., Design, Setting, and Participants: This double-masked randomized clinical trial screened 117 consecutive pediatric patients aged 3 to 12 years with American Society of Anesthesiologists physical status I to II undergoing elective MRI under deep sedation from November 2, 2022, to April 28, 2023, at a tertiary referral center. Four patients met the exclusion criteria, and 5 patients refused to participate. The participants and outcome assessors were masked to the group allocation., Interventions: During the MRI, the propofol group received 0.2 mL/kg of 1% propofol and 2 mL of 0.9% saline followed by a continuous infusion of propofol (200 μg/kg/min) and 0.9% saline (0.04 mL/kg/min). The propofol-ketamine group received 0.2 mL/kg of 0.5% propofol and 1 mg/kg of ketamine followed by a continuous infusion of propofol (100 μg/kg/min) and ketamine (20 μg/kg/min)., Main Outcome and Measure: The incidence of atelectasis assessed by lung ultrasonography examination., Results: A total of 107 children (median [IQR] age, 5 [4-6] years; 62 male [57.9%]), with 54 in the propofol group and 53 in the propofol-ketamine group, were analyzed in this study. Notably, 48 (88.9%) and 31 (58.5%) patients had atelectasis in the propofol and propofol-ketamine groups, respectively (relative risk, 0.7; 95% CI, 0.5-0.8; P < .001). The incidence of desaturation and interruption of the MRI due to airway intervention or spontaneous movement did not significantly differ between the groups. The propofol-ketamine group showed a faster emergence time than the propofol group (15 [9-23] vs 25 [22-27] minutes in the propofol-ketamine vs propofol group; median difference in time, 9.0 minutes; 95% CI, 6.0-12.0 minutes; P < .001). No patient was withdrawn from the trial due to adverse effects., Conclusions and Relevance: In this randomized clinical trial, the propofol-ketamine combination reduced sedation-induced atelectasis while allowing for faster emergence compared with propofol alone., Trial Registration: cris.nih.go.kr Identifier: KCT0007699.

Background: Real-world data on medications used for conditions other than inflammatory bowel disease (IBD) are sparse. We examined how the onset of IBD affects the prescription pattern of selected non-IBD medication and the risk of becoming an incident user., Methods: This nationwide cohort study utilized data from Danish health registers. We included incident patients with young adult-onset IBD (18-39 years of age), adult-onset IBD (40-59 years of age), and elderly-onset IBD (60+ years of age), from 1998 to 2018 and followed all for 3 years. We examined redeemed prescriptions before and after the onset of IBD and estimated the risk of becoming a user of non-IBD medications using logistic regression models., Results: We identified 36165 patients, 16 771 (46%) with young adult onset, 10615 (29%) with adult onset, and 8779 (24%) with elderly onset. The onset of IBD increased the use of antidepressants, antipsychotics, sedatives/hypnotics, opioids, nonopioid analgesics, antidiabetics, and proton pump inhibitors, even in patients with no other underlying comorbid diseases. The adjusted odds ratio for using antidepressants 1 year after the onset of IBD in elderly was 1.50 (95% confidence interval [CI], 1.14-1.82), in opioids 1.69 (95% CI, 1.45-1.95), in nonopioid analgesics 2.10 (95% CI, 1.77-2.48), in cardiovascular medication 2.20 (95% CI, 1.86-2.61), and in proton pump inhibitors 1.51 (95% CI, 1.31-1.74) compared with adults., Conclusions: In all 3 age groups, the proportions of patients with redeemed prescriptions for several groups of non-IBD medication were significantly increased after the IBD diagnosis compared with before. The risk of becoming an incident user for several groups of non-IBD medication was increased in elderly patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

There is a high incidence of postoperative sleep and sleep architecture disorders in patients undergoing surgery, and dexmedetomidine (DEX) is commonly used to improve postoperative sleep quality and ameliorate the adverse effects of poor sleep on various organ systems. The continuous intraoperative intravenous infusion of DEX, the addition of DEX to postoperative intravenous analgesia pumps, and the continuous infusion of DEX after admission to the intensive care unit are often used clinically to improve postoperative sleep quality at doses of 0.1 to 0.7 μg/kg/hour, but the effects of DEX on sleep quality and structure identified in these studies have been inconsistent. Thus, it is unclear whether DEX improves postoperative sleep quality. The various methods of administering DEX to improve postoperative sleep quality have differing effects, the route used modifies the effect of DEX on sleep structure, and the intrinsic mechanism whereby DEX improves sleep quality remains to be fully investigated. In the present review, we describe new directions for future research into the effects of DEX on postoperative sleep quality and the mechanisms involved, which should help guide the design of further studies. This narrative review was completed according to the Scale for the Assessment of Narrative Review Articles (SANRA)., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Rationale: Zolpidem, a non-benzodiazepine sedative-hypnotic, is considered safer for the treatment of insomnia compared to benzodiazepines. However, in recent years, there have been growing reports of Zolpidem dependence, addiction, and withdrawal symptoms. We reported a case of Zolpidem addiction and successful detoxification, reviewed similar cases in the literature, and proposed a potential mechanism underlying Zolpidem addiction., Patient Concerns: The patient was a 46-year-old Tibetan woman who had been using Zolpidem intermittently to treat insomnia for at least 8 years. She was overweight, with a BMI of 28.04 kg/m², and had hypertension, diabetes, a 20-year smoking history, and several years of alcohol abuse, often seeking instant gratification. She voluntarily increased both the dosage and frequency of Zolpidem, experiencing euphoria, anxiolysis, and increased appetite at higher doses, which led her to gradually escalate her dosage to 280 mg per day in divided doses. However, upon stopping Zolpidem, she experienced withdrawal symptoms, including insomnia, tension, and palpitations., Diagnoses: She was diagnosed with a combination of hypnotic use disorder, anxiety disorder, hypertension, and diabetes., Interventions: She underwent diazepam replacement therapy, along with antianxiety medications and mindfulness-based cognitive therapy, to address Zolpidem addiction., Outcomes: After 13 days of inpatient treatment, the patient successfully quit Zolpidem. During a 3-month follow-up, she returned to work and remained free from Zolpidem use., Lessons: We speculate that Zolpidem addiction is likely linked to the drug's euphoric effects and certain patient characteristics, such as sensation-seeking behavior. A comprehensive approach, involving both pharmacological and psychological interventions, is essential for an effective detoxification strategy for Zolpidem addiction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Although the use of benzodiazepine receptor agonists is a risk factor for falls and fractures, whether benzodiazepine-avoiding hypnotic bundles are beneficial in clinical settings remains unclear., Methods: A new hospital-wide standardized hypnotic bundle for insomnia, with suvorexant as the first choice, was created for clinical purposes. This single-center retrospective cohort study involved a pre-post design and adult inpatients who had had falls. The primary outcome was the total fall rate in the pre-post groups. Additionally, the level change in the fall-rate trend for each month at standardization of the new hypnotic bundle was analyzed. The numbers of hypnotic-related falls and injuries requiring treatment were evaluated., Results: There were no differences in baseline characteristics between the two groups, except for patients with COVID-19. Overall, 31 736 patients were included in this study. The total number of falls was 924 (3.42‰) in the pre-standardization group and 837 (3.31‰) in the post-standardization group, with no significant difference. An interrupted time-series analysis of the level change in the fall rate revealed that the gap in trend at standardization was -11%, with no significance. Hypnotic-related falls were 300 (1.11‰) versus 213 (0.84‰), and the injury incidences were 251 (0.93‰) versus 181 (0.71‰) in the pre and post groups, respectively, showing a significant reduction., Conclusions: The standardization of the new hypnotic bundle for insomnia did not help achieve a significant reduction in total falls. However, our findings suggest that this bundle has the potential to reduce hypnotic-related falls and injuries in inpatients who have had falls. Geriatr Gerontol Int 2024; 24: 1144-1149., (© 2024 Japan Geriatrics Society.)

Introduction: Neonates in a NICU experience pain. Based on the cardiovascular and nociceptive systems link, a Newborn Infant Parasympathetic Evaluation (NIPE) monitor was designed to assess pain. The use of α 2 -agonists as analgesic-sedative drugs has increased in neonates. Given their effect on the autonomic system, we hypothesized that their use may alter NIPE's measurement capacity., Methods: Data were prospectively collected. The included patients were evaluated using combined pain assessment systems., Results: Sixteen newborns requiring sedoanalgesia underwent a total of 84 pain assessments. A good correlation was found between the NIPE-index and the COMFORT-neo and the crSO2 (cerebral regional oxygen saturation). No correlation was found in premature infants. By sedation group, the correlation remained in those receiving α 2- agonist., Conclusion: NIPE is a reliable tool for pain assessment. Further studies in premature infants are needed. The use of α 2- agonist does not alter the measuring capacity of NIPE. The correlation between NIPE-index and crSO2 was also demonstrated., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: This study aims to estimate the extent to which anticholinergic and sedative burden is associated with cognitive ability and self-reported cognitive difficulties (SCD) in middle-aged and older adults living with HIV., Design: This cross-sectional analysis examined data from the inaugural visit of participants enrolled in the Positive Brain Health Now (BHN) study., Methods: Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM; higher is better) and SCD using the Perceived Deficits Questionnaire (PDQ; higher is worse). Medication burden was quantified using several scoring systems, including the Anticholinergic Cognitive Burden (ACB), Anticholinergic and Sedative Burden Catalog (ACSBC), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and the Sedative Load Model (SLM). Multivariable Ordinary Least Squares and quantile regression were utilized to estimate average effects and distribution-specific impacts, respectively., Results: Of 824 participants (mean age 53 years, 84.7% men), 41.4% used anticholinergics (ACSBC) and 39% used sedatives (SLM). High anticholinergic burden was linked to worse cognitive ability [ β = -3.81; 95% confidence interval (CI): -7.16, -0.46] and SCD ( β = 3.89; 95% CI: 1.08, 6.71). Using three or more anticholinergics worsened cognitive ability ( β = -4.45; 95% CI: -8.54, -0.35), and using three or more sedatives increased SCD ( β  = 4.35; 95% CI: 0.92-7.78). Stronger negative associations were observed in participants with lower cognitive ability and more difficulties., Conclusions: These results suggest that anticholinergic and sedative burden may contribute to cognitive impairment in people with HIV. Personalized medication management and regular cognitive assessments could mitigate these adverse effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Xylazine, a veterinary sedative, has emerged as a concerning element in the landscape of substance use in the United States. This integrative review synthesizes evidence from a systematic examination of 14 selected studies conducted between 2008 and 2023. The primary objective is to comprehensively understand the epidemiology and prevalence of xylazine use, particularly its involvement in drug-related deaths, regional variations, national impact, co-occurrence with opioids, and challenges associated with detection and intervention. The results underscore stark regional disparities in xylazine prevalence. West Virginia and Miami-Dade County have experienced alarming surges in xylazine-involved drug-related deaths. Nationally, its influence extends beyond regional boundaries, predominantly affecting white males in the Northeast. The co-occurrence of xylazine with opioids, especially fentanyl and heroin, significantly amplifies the risks of fatal overdoses. Detecting xylazine presents formidable challenges due to its frequent presence alongside other substances, necessitating enhanced surveillance and more effective detection methods. User perspectives emerge as pivotal, emphasizing the importance of user-informed harm reduction strategies. In conclusion, this review has significant policy implications. Tailored, region-specific strategies are imperative to address the diverse prevalence of xylazine use. A nationwide response is indispensable, prioritizing harm reduction initiatives, enhanced detection methods, and active user engagement. The multifaceted nature of the xylazine issue requires comprehensive approaches to mitigate its profound risks effectively. Policymakers are urged to consider regional disparities and the co-occurrence of xylazine with opioids when crafting targeted interventions. Immediate, user-informed harm reduction is vital to address the evolving landscape of xylazine use in the United States.

Background: Transbronchial lung cryobiopsy (TBLC) has emerged as a promising diagnostic tool for interstitial lung disease (ILD). This study aimed to assess the initial experience, procedural learning curve, and influence of sedative medications on complication rates, particularly bleeding and pneumothorax, in the implementation of a TBLC program for ILD diagnosis., Methods: In this retrospective cohort study, we analysed 119 patients who underwent TBLC at Nippon Medical School Hospital from April 2021 to March 2024. Procedural times, complication rates, and histopathological outcomes were evaluated. The learning curve was assessed using cumulative sum (CUSUM) analysis, focusing on procedure time and biopsy yield. The association between sedative medication dosages and bleeding risk was also examined., Results: The overall diagnostic yield was high, with alveolar tissue obtained in 97.5% of cases and a definitive pathological diagnosis achieved in 81.5% of patients. CUSUM analysis revealed a proficiency threshold at approximately 56 cases, with improved efficiency and biopsy yield in the consolidation phase. Fentanyl dosage was significantly associated with reduced bleeding complications (odds ratio 0.51, 95% confidence interval 0.27-0.97, p = 0.041)., Conclusions: TBLC is a safe and effective diagnostic tool for ILDs, with a manageable learning curve for procedural efficiency. Sedation, particularly fentanyl dosage, may plays a crucial role in minimizing complications, but further research is needed to clarify this relationship. These findings support the adoption of TBLC as a standard diagnostic approach for ILD and highlight the importance of adequate training and optimized sedation protocols to ensure safety and efficacy in clinical practice., (© 2024. The Author(s).)

Background: Respiratory depression is a common complication during operative procedures, meanwhile, ciprofol can provide effective sedation for surgical operations. However, there is not enough evidence to prove the advantage of ciprofol in reducing respiratory depression. So, this meta-analysis aimed to assess the efficacy of ciprofol on the incidence of respiratory depression compared with propofol., Methods: Two individual researchers conducted searches for randomized controlled trials in PubMed, Embase, and Cochrane Central Register of Controlled Trials. The meta-analysis was performed using Review Manager software., Results: Seven trials with a total of 1408 patients were included in this meta-analysis. The results showed that ciprofol could reduce the incidence of respiratory depression compared with propofol (risk difference [RD] = -0.09, 95% confidence interval [CI]: -0.15 to -0.04). Ciprofol significantly reduced the incidence of respiratory depression when the method of administration was intravenous injection (RD = -0.06, 95% CI: -0.10 to -0.03), or continuous infusion (RD = -0.30, 95% CI: -0.45 to -0.15). Meanwhile, ciprofol significantly reduced the incidence of respiratory depression with the dosage not only greater than or equal to 0.4 mg/kg (RD = -0.11, 95% CI: -0.20 to -0.02), but also <0.4 mg/kg (RD = -0.08, 95% CI: -0.13 to -0.02). And ciprofol significantly reduced the incidence of hypoxemia (risk ratio [RR] = 0.47, 95% CI: 0.28 to 0.80), injection pain (RD = -0.32, 95% CI: -0.46 to -0.17), body movement (RR = 0.60, 95% CI: 0.43 to 0.84), dizziness (RR = 0.75, 95% CI: 0.62 to 0.90). Finally, ciprofol did not increase awakening time (standard mean difference [SMD] = 0.15, 95% CI: -0.02 to 0.31)., Conclusion: From this meta-analysis, it is demonstrated that ciprofol might reduce the incidence of respiratory depression and injection pain. These benefits are important in surgery to ensure safe and rapid postoperative recovery. So, ciprofol may be a safe and appropriate drug with fewer adverse effects used in clinical anesthesia., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

This commentary on a case describes how social determinants of health also contribute to insomnia and then suggests how to balance risks and benefits of different strategies for managing chronic insomnia. Behaviorally induced insufficient sleep syndrome can exacerbate morning side effects of prescription sleep aids, and there are potentially serious long-term risks (eg, dementia, falls, death) associated with chronic benzodiazepine use. Before trying sleeping pills, chronic insomnia should be treated with cognitive behavioral therapy., (Copyright 2024 American Medical Association. All Rights Reserved.)

Objectives: The use of intranasal (IN) analgesics and sedatives has been studied among pediatrics patients in the emergency department and outpatient settings. However, less is known about their usage in inpatient settings. This study aims to evaluate the indications and safety profile for IN fentanyl and midazolam usage in pediatric patients admitted to a large tertiary care children's hospital., Methods: This study is a retrospective chart review of admitted patients receiving IN fentanyl and/or midazolam over a 6-year period. Indications for medication use, medication dosages, patient characteristics, and any serious adverse drug reactions were recorded. Reported serious adverse outcomes include use of reversal agents as well as any documented respiratory depression, hypotension, or need for escalation of care., Results: Of 156 patients included, 119 (76%) received IN midazolam alone, 20 (13%) patients received IN fentanyl alone, and 17 (11%) patients received both medications. The most common applications for IN medication administration were nasogastric tube placements (n = 62), peripheral intravenous line insertions (n = 30), peripherally-inserted central catheter placements (n = 23), and lumbar punctures (n = 16). No serious adverse events were reported., Conclusions: This study suggests that IN fentanyl and midazolam were administered to pediatric inpatients undergoing routine procedures without serious adverse drug reactions being reported. Although these findings are encouraging, more prospective studies are needed before wider implementation of IN fentanyl and midazolam administration in pediatric inpatients., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations. The funding organizations had no role in the design, preparation, review, or approval of this paper., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Both Alzheimer's disease (AD) and deliriogenic medications increase the risk of delirium in older adults. This study examined the association between delirium and the subsequent monthly use of anticholinergic, sedative, and opioid medications in the 1 year after delirium in older adults with AD., Methods: This comparative interrupted time series analysis involved adults (aged 65 years and older) with a diagnosis of AD initiating on cholinesterase inhibitors (ChEIs) based on 2013-2017 Medicare data. Separate patient-level segmented regression models were used for each outcome to evaluate changes in the cumulative anticholinergic burden (CAB), sedative load, and opioid load after the delirium/index event using a 12-month baseline and follow-up period among patients who had a delirium event and those without delirium (control group). Propensity score-based stabilized weights were utilized to balance baseline factors in the delirium and control groups., Results: The study included 80,019 older adults with AD with incident ChEI use; 17.11% had delirium. There was an immediate decline in monthly CAB after the delirium event (mean estimate -0.86, p-value: 0.01) compared to the control group. A similar decline was observed when examining the sedative load (-0.06, p-value: 0.002) after the delirium event. However, there was no decline in opioid load (-0.50, p-value: 0.18). In the long term, CAB (0.13; p-value: <0.0001), sedative load (0.01; p-value: <0.001), and opioid load (0.07; p-value: 0.006) increased over the 1-year post-delirium period in the delirium group compared to those without delirium., Conclusion: This study found the burden of deliriogenic medications over the 1-year follow-up showed increasing trends in older adults with AD, even though there was some level shift in CAB and sedative load after the delirium event., (© 2024 Pharmacotherapy Publications, Inc.)

The Aim of the Present Study: The aim of the present study was to do a comparison of the recovery profiles and airway-related adverse events of pediatric magnetic resonance imaging (MRI) sedation patients who received propofol alone to those who received midazolam alone., Methods: This retrospective cohort study was approved by the Mutah University Ethical Approval Committee (No. 2378). A search of the patients' medical records was performed between September 2021 and April 2022 to identify children aged 4 months-11 years who received propofol or midazolam for MRI sedation. The patients were subdivided into two groups: Those who had propofol alone (propofol group) and those who received midazolam (midazolam group) for pediatric MRI sedation. In propofol group, a 1-2 mg/kg of propofol bolus was given to have a deep sedation (Ramsay Sedation Scale score of 5). Patients in midazolam group received 0.05 mg/kg of midazolam. During the maintenance state of sedation, the patient received 150 µg/kg/min of propofol, and the infusion rate was adjusted in 25 μg/kg/min increments up or down at the discretion of the anesthesiologists to maintain a state of deep sedation. The major targets of this study were recovery profiles (time to awake and time to discharge) and airway-related intervention ratios in pediatric MRI sedation patients. Patient demographics, MRI sedation, and recovery data, including propofol induction dose, airway intervention, and sedation-related adverse events from the pediatric sedation recovery unit were also collected., Results: The mean (standard deviation [SD]) propofol induction dose was higher compared to midazolam group (2.4 [0.7] mg vs. 1.3 [0.5] mg; mean difference, 1.1 mg; P < 0.001). The mean (SD) infusion rate was higher in propofol group compared to midazolam group (161.3 [37.6] μg/min/kg vs. 116.2 [25.6] μg/min/kg; mean difference 45.1 μg/min/kg; P < 0.001). The mean (SD) propofol total dose was higher in propofol group compared to midazolam group (236.3 [102.4] mg vs. 180.7 [80.9] mg; mean difference, 155.4 mg; P < 0.001). The mean (SD) time to awake was longer in midazolam group compared to propofol group (21.2 [5.6] min vs. 23.0 [7.1] min; mean difference, 1.8 min; P < 0.001). The mean (SD) time to discharge was longer in midazolam group compared to propofol group (34.5 [6.9] min vs. 38.6 [9.4] min; mean difference, 4.1 min; 95% confidence interval, 3.0-5.1; P < 0.001)., Conclusion: The administration of midazolam during pediatric MRI sedation can decrease the frequency of airway complications without prolonging the clinically significant recovery profile., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research., Methods: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities., Results: Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied., Conclusion: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence., (© 2024 Acta Anaesthesiologica Scandinavica Foundation.)

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea., Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications., Results: A total of 6,691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1,457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225/1457] vs. 6.2% [322/5234]; P < 0.001, odds ratio: 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05)., Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

Objectives: Pediatric patients with extremity fractures often require sedation for fracture reduction in the pediatric emergency department (PED). Although orthopedic literature suggests combination sedation regimens may be more effective for fracture reduction, some pediatric literature suggests adverse events are more frequent. The primary objective of this study is to determine the comparable depth of sedation and incidence of adverse events when intravenous ketamine is used alone versus with midazolam for pediatric procedural sedation and orthopedic fracture reduction., Methods: This is a retrospective cohort study of pediatric patients 2-18 years old who underwent sedation for fracture reduction in the PED at a single level 1 trauma center over a 2-year period. Medical records were reviewed, and occurrence of adverse events, depth of sedation (Ramsey score), midazolam dose, total ketamine administration, opiate administration, total sedation time, and time to PED discharge were compared in patients who received ketamine alone versus those who received ketamine with midazolam. Logistic regression models were adjusted to evaluate for potential confounders., Results: There was a statistically significant increase in the occurrence of hypoxia with coadministration of midazolam (5% vs 0%). When hypoxia occurred, it was mild and resolved with repositioning or administration of supplemental oxygen. Length of sedation was increased in sedations with coadministration of benzodiazepines by approximately 3.5 minutes. Time to PED discharge was not significantly different. There was no significant difference in depth of sedation, ketamine dose administered, end-tidal CO 2 measurements, administration of positive pressure ventilation, vomiting, agitation, or overall occurrence of adverse events. No patients developed apnea or laryngospasm., Conclusions: This study showed a low rate of adverse events in pediatric sedation for orthopedic reduction with ketamine alone or ketamine with midazolam. There was an increased occurrence of hypoxia with coadministration of midazolam and an increase in the length of sedation. This study showed no difference in depth of sedation based on Ramsay scores when midazolam was coadministered. Information on the orthopedic reduction and provider satisfaction was not collected., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The Coronavirus disease 2019 (COVID-19) pandemic markedly influenced mental health care practices, notably regarding electroconvulsive therapy (ECT). This was due to the redistribution of anesthetic agents used during ECT such as propofol, for intensive care units. Because in our center propofol was switched to etomidate to avoid ECT activity discontinuation, we undertook this study in order to compare Propofol and Etomidate regarding electroencephalographic seizure duration and stimulus intensity., Methods: We performed a retrospective and comparative study, each patient being its own control. We included patients with at least two courses of ECT on propofol and two others with etomidate over the period from September 2019 to April 2021, regardless of the psychiatric diagnosis. Our data collection process notably targeted stimulus intensity, seizure duration recorded using electroencephalography, and medication used for anesthetic induction., Results: Overall, we included 18 patients with a male: female ratio of 1:2.6 and a mean (and standard deviation) age of 62.7±13.4 years. We found that the mean intensity of stimulation was significantly lower with etomidate when compared to propofol (425.3±250.0 vs. 658.9±280.2 mC, P=0.001). The mean duration of electroencephalographic seizure was significantly higher with etomidate in comparison to propofol (53.5±16.6 vs. 35.0±12.2seconds, P<0.001)., Conclusion: By using each patient as its own control, our study found that etomidate, while compared to propofol, was related to a lower level of stimulatory intensity and a longer electroencephalographic seizure duration., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Emergence agitation (EA) is an adverse complication during early recovery from sevoflurane anesthesia. Continuous intravenous infusion of dexmedetomidine (DEX) is commonly used for EA prevention. However, a wide dose range is used for preventing EA, and the optimal dose remains unknown. This study was aimed at determining the optimal dose (the 90% effective dose [ED90]) of DEX for continuous intraoperative infusion for EA prevention in children., Methods: We enrolled children aged 3 to 7 years who underwent dental treatment under sevoflurane anesthesia. DEX was continuously infused from the time of the establishment of the intravenous access until 5 minutes before the end of surgery. The initial DEX dose was 0.5 µg/kg/h, and subsequent dose adjustments were determined based on the response of the previous patient by using an up-down sequential allocation with a biased-coin design. The primary outcome was the ED90 for continuous DEX infusion based on the success or failure of the EA-preventing dose., Results: Forty-five patients were enrolled in the study. The DEX dose ranged from 0.50 to 0.90 µg/kg/h. The estimated ED90 (95% confidence interval [CI]) for preventing EA was 0.74 µg/kg/h (0.67-1.05 µg/kg/h). The duration of surgery (mean ± standard deviation [SD]) was 113 ± 30 minutes. The times (mean ± SD) for extubation, time to emergence, and recovery time were 5 ± 2 minutes, 27 ± 9 minutes, and 39 ± 7 minutes, respectively., Conclusions: The ED90 for continuous intraoperative DEX infusion for EA prevention in pediatric patients receiving dental treatment under sevoflurane anesthesia was 0.74 µg/kg/h (95% CI, 0.67-1.05 µg/kg/h)., (Copyright © 2023 International Anesthesia Research Society.)

Background: Rapid sequence intubation (RSI) is a crucial step in the resuscitation process for critically ill patients, and the judicious use of sedative drugs during RSI significantly influences the clinical outcomes of patients. Ketamine is a commonly used anesthetic sedative; however, its impact on the mortality of patients undergoing RSI has yielded inconsistent findings. Therefore, we conducted a systematic review and meta-analysis investigating ketamine's role in RSI to provide insights into selecting appropriate sedatives for critically ill patients., Methods: In this systematic review and meta-analysis, we conducted a systematic search on MEDLINE (PubMed), Embase, and Cochrane Central Register of Controlled Trials, without restricting to randomized controlled trials (RCTs) or cohort studies. The search was performed from inception until Dec 12, 2023, with no language restrictions. All studies comparing the use of sedatives, including ketamine, and documenting in-hospital mortality were included in this study., Results: A total of 991 studies were identified, out of which 15 studies (5 RCTs and 10 cohort studies) involving 16,807 participants fulfilled the inclusion criteria. No significant impact on in-hospital mortality was observed with the use of ketamine compared to other drugs during RSI (OR 0.90, 95%CI 0.72 to 1.12). Low-quality evidence suggested that ketamine might reduce mortality within the first seven days of hospitalization (OR 0.42, 95%CI 0.19 to 0.93), but it may also have a potential effect on prolonging ICU-free days at day 28 (MD -0.71, 95%CI -1.38 to -0.05). There were no significant differences in the results of the other RSI-related outcomes, such as physiological function and adverse events., Conclusions: Based on existing studies, ketamine showed no significant difference compared to other sedatives in terms of in-hospital mortality, physiological impact, and side effects following RSI. However, it may reduce mortality within 7 days while probably prolong the length of stay in the ICU., Trial Registration: CRD42023478020., (© 2024. The Author(s).)

Objective: To evaluate the effect of propofol, sevoflurane, and dexmedetomidine on respiratory complications in children undergoing fiberoptic bronchoscopy (FOB)., Methods: This double-blind randomized clinical trial was conducted among 120 children aged 1 month to 3 years undergoing FOB. The patients were randomized into 3 groups ( n =40) for anesthesia induction with sevoflurane inhalation, 1 mg/kg propofol, or 1 μg/kg dexmedetomidine before bronchoscopy, and the changes in hemodynamic parameters, sedation level, and respiratory complications during and after the procedure were assessed., Results: The patients' heart rate during bronchoscopy was significantly lower and the mean arterial blood pressure significantly higher in dexmedetomidine group than in sevoflurane and propofol groups ( P < 0.05). Cough during bronchoscopy did not occur in any of the cases in propofol group, while the highest frequency of cough was recorded in dexmedetomidine group. The incidence of laryngospasm in the propofol group (12.5%) was significantly lower than those in sevoflurane and dexmedetomidine groups (30% and 32.5%, respectively) ( P < 0.05)., Conclusion: Sevoflurane and propofol are safe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve better sedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

Background: Emergence delirium (ED) is a common occurrence in pediatric postanesthesia events, leading to negative outcomes. Dexmedetomidine (DEX), as an anesthesia adjuvant, has shown promise in preventing ED in adult surgeries, and it has been increasingly used in pediatric surgical settings. However, its effectiveness in other postanesthesia events, such as MRI examinations and ambulatory surgery centers, remains unclear. This meta-analysis aims to assess the safety and efficacy of DEX in preventing ED in various pediatric postanesthesia events beyond surgery., Methods: Prospective randomized controlled trials were searched in Pubmed, Web of Science, and EBSCO until October 13, 2023. Comparisons were made between DEX and other sedatives or analgesics in different postanesthesia events (including surgery operations, the examination of MRI, day surgery, and invasive action). Subgroup analyses were conducted based on drug delivery methods, medication timing, DEX dosages, use of analgesics, event types, and recovery time., Results: A total of 33 trials involving 3395 patients were included. DEX significantly reduced the incidence of ED (odds ratios [OR] = 0.23, 95% confidence interval [CI]: 0.19-0.27, I2 = 37%, P < .00001). Intranasal delivery of DEX was the most effective (OR 0.18, 95% CI: 0.10-0.32, P < .00001, I2 = 0%). DEX also showed benefits in day surgery and mask insertion events (OR 0.30, 95% CI: 0.14-0.26, P = .001, I2 = 0%)., Conclusion: DEX demonstrates superior efficacy in preventing ED in pediatric postanesthesia events compared to other sedatives and analgesics. Its use is recommended in various settings for its safety and effectiveness in managing ED., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To compare the efficacy and safety of ciprofol, propofol, propofol and etomidate mixture or ciprofol and etomidate mixture in patients undergoing painless gastroscopic anesthesia, and to explore the optimal plan to relieve the patient's discomfort., Methods: A total of 120 patients scheduled for painless gastroscopy were randomly assigned to 4 groups: propofol (Group P), ciprofol (Group C), propofol-etomidate mixture (Group P-E), and ciprofol-etomidate mixture (Group C-E). The success rate of gastroscopy examination, patient satisfaction, incidence of injection pain, hemodynamic parameters, induction time, procedure time, the consumption of drugs, awakening time, and incidence of adverse events were evaluated., Results: All patients in the study successfully completed the gastroscopy. The satisfaction of patients in Group C-E was significantly higher than that in Group P (P < .05), but there was no statistical significance in the patient satisfaction among the other groups. Compared with Group P, the incidence of injection pain in Groups C and C-E significantly decreased (P < .05). There were no significant differences in the SBP, diastolic blood pressure, HR, and SpO2 among the 4 groups (P > .05). The awakening time of Group C was significantly longer than that of Groups P and P-E (P < .05), but there was no statistically significant difference in the awakening time of other groups., Conclusion: Ciprofol demonstrated efficacy in inducing sedation or anesthesia during painless gastroscopy that was similar to propofol, while exhibiting a comparable safety profile. Moreover, the combination of propofol and etomidate, as well as the combination of ciprofol and etomidate, were both shown to be equally safe and effective for this clinical application. These findings suggest that ciprofol can be considered as a safe and effective alternative for painless gastroscopy, and the ciprofol-etomidate mixture may be a better choice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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

Background: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults., Methods: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2-7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance., Results: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years., Conclusions: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia., Trial Registration Numbers and Dates of Registration: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017., (© 2024. The Author(s).)

Background: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication., Objective: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations., Methods: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures., Results: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures., Conclusion and Relevance: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU)., Objective: We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children., Methods: We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium., Results: A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group., Conclusion: The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Procedural sedation is crucial in gastrointestinal endoscopy, where propofol is commonly used but may lead to cardiovascular and respiratory side effects. Remimazolam, a new drug, offers advantages such as rapid onset and recovery. The sedation protocols for this population vary, requiring tailored titration of sedatives. The comparative safety of these drugs in elderly patients undergoing procedural sedation remains unclear, as previous studies primarily focus on the general population. We aimed to compare the safety profiles of remimazolam and propofol in this context. in elderly patients undergoing procedural sedation for gastrointestinal endoscopy., Evidence Acquisition: We searched MEDLINE, EMBASE and Cochrane Library for randomized controlled trials (RCTs) comparing propofol with remimazolam in elderly patients undergoing procedural sedation. Our outcomes were the incidence of adverse effects. A trial sequential analysis (TSA) was conducted on all outcomes to assess the adequacy of the sample size in supporting our findings., Evidence Synthesis: We selected seven RCTs including 1499 patients, of whom 764 (50.96%) were randomized to receive remimazolam. Remimazolam exhibited a significantly lower risk of adverse events, including hypoxemia, respiratory depression, hypotension, bradycardia, and injection pain, compared to propofol. Incidences of PONV, dizziness and headache, did not significantly differ between the groups. The findings of the TSA indicated that our sample size was sufficiently large to render further studies inconsequential for most outcomes., Conclusions: Our findings suggest that in elderly patients having gastrointestinal endoscopy, remimazolam could be safer than propofol. This population may benefit from remimazolam's lower risk of adverse events, notably hypoxemia and respiratory depression.

Constipation is a prevalent gastrointestinal disorder that affects people globally, decreasing their quality of life and life expectancy. Individuals with schizophrenia often suffer from constipation, which could be a result of the illness itself or the side effects of psychotropic medications. However, little research has been conducted on factors contributing to constipation in individuals with schizophrenia. To address this issue, we conducted a survey using self-administered questionnaires and medical records to identify factors associated with constipation in psychiatric outpatients. This study included 399 patients with schizophrenia, resulting in a high prevalence of constipation (43.4%). The analysis suggested that female gender, the doses of antiparkinsonian medications, and benzodiazepine sleeping pills may be associated with constipation., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background: Anticholinergic (AC) and sedative medications are a risk factor for cognitive impairment. This study sought to characterize AC and sedative use in older patients seen for outpatient neuropsychological evaluation and evaluate their associations with different cognitive domains. We hypothesized that AC and sedative use would be associated with worse attention/processing speed (AP), executive functioning (EF), and memory., Methods: We conducted a cross-sectional chart review of 392 patients (mean [M] age = 72 ± 7.7 years, range = 54-91). Medications were characterized by number of AC medications (≥1 on the Anticholinergic Cognitive Burden Scale [ACB]), number of sedative medications, and polypharmacy (≥5 daily medications). Demographically adjusted composites were calculated for AP, EF, and memory. Bivariate Pearson correlations assessed relationships between medication use and cognition. Multivariate linear regressions evaluated significant medication-cognition associations, controlling for total medications, medical comorbidities, and estimated premorbid cognitive functioning., Results: Polypharmacy was common (80%; n = 314). Most patients (70%; n = 275) used ≥1 sedative medications (range = 0-9). Over half (63%; n = 248) used ≥1 AC drugs (range = 0-7), yet ACB scores were ≤2 in 74% of patients. Sedative use was negatively correlated with AP (r = -0.134, p = 0.008) and EF (r = -0.105, p = 0.04). ACB scores were negatively correlated with AP (r = -0.106, p = 0.037). Sedatives and a priori covariates significantly predicted AP performance (R 2  = 0.127, p < 0.001); using more sedative medications was uniquely associated with worse AP (β = -0.426, p = 0.049). No significant associations were found with memory., Conclusion: AC and sedative medications and polypharmacy were prevalent in this sample of older patients. Though both drug classes had negative relationships with AP and EF, sedatives had a particularly negative association with AP. Contrary to our hypotheses, memory was not associated with medication use; however, anticholinergic burden was low within the sample, and AP and EF deficits may masquerade as memory problems., (© 2024 The American Geriatrics Society.)

Background: Prescribing of gabapentinoids and Z-drug-hypnotics has increased in the population and among people receiving opioid-agonist treatment (OAT) for opioid dependence. Evidence is mixed on whether co-prescribing of sedatives such as gabapentinoids and Z-drugs during OAT increases risk of drug-related death (DRD)., Methods: We conducted a retrospective cohort study of individuals prescribed OAT between 2011 and 2020 in Scotland. Prescribing records were linked to mortality data and other healthcare datasets (sociodemographic, comorbidity). We identified episodes of treatment with gabapentinoids/Z-drugs and used multivariable quasi-Poisson regression to model associations between co-prescription and DRD risk., Results: Among 46,602 individuals with 304,783 person-years of follow-up, we found that co-prescription was common, with 25 % and 34 % ever being co-prescribed gabapentinoids and Z-drugs, respectively. Gabapentinoid exposure was strongly associated (adjusted hazard ratio (aHR)=2·18, 95 % CI=1·92, 2·46) and Z-drug exposure moderately associated (aHR=1·39, 95 % CI=1·15, 1·66) with elevated risk of DRD. Gabapentinoid exposure was associated with DRD risk on and off OAT; Z-drug exposure was less strongly associated with DRD risk when on OAT., Conclusions: Co-prescription of gabapentinoids and Z-drugs is common among OAT patients. However, co-prescription is associated with increased risk of DRD. Alternatives to prescribing sedative medications to OAT patients and/or greater monitoring - if prescribed - are needed., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Study Objective: Remimazolam's benefits for patients undergoing painless flexible fiberoptic bronchoscopy remain uncertain. We aimed to compare the efficacy and safety of remimazolam and dexmedetomidine in flexible fiberoptic bronchoscopy (FFB)., Design: Randomized controlled trial., Setting: University hospital., Patients: Between April 2021 and September 2022, patients undergoing painless flexible fiberoptic bronchoscopy were recruited., Interventions: The patients were randomly assigned with a 1:1 ratio to remimazolam-remifentanil group (RR group) or dexmedetomidine-remifentanil group (DR group)., Measurements: The primary outcome was the procedure interruption rate during bronchoscopy. Secondary outcomes were hemodynamic changes, resuscitation time, rescue medication usage rate and dose, satisfaction scores of patients and bronchoscopists, operation-related complications, and adverse events., Main Results: A total of 363 patients were included for final analysis. The interruption rates of bronchoscopy were 8.2 % in the RR group and 39.2 % in the DR group (P < 0.05). The rescue medication usage rate (4.4 % vs. 38.7 %, P < 0.05) and dose (1.51 ± 8.15 mg vs. 13.17 ± 18.86 mg, P < 0.05) were lower in the RR group compared with the DR group. The incidence of oxygen desaturation was significantly lower in the RR group than in the DR group (14.3 % vs. 44.2 %, P < 0.05). Hemodynamic changes in patients in the DR group were significant, with longer recovery time and lower satisfaction scores for both inpatients and bronchoscopists (P < 0.05), compared with the RR group. However, there were no significant differences between groups in terms of operation-related complications (P > 0.05) except for postoperative dizziness, which was more common in the DR group (P < 0.05)., Conclusions: Remimazolam is effective and safe in painless flexible fiberoptic bronchoscopy. It allows a lower procedure interruption rate and incidence of oxygen desaturation, providing better hemodynamic stability compared to dexmedetomidine., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We explored the effects of dexmedetomidine (DEX) versus propofol on outcomes in critically ill patients and to assess whether these effects are dissimilar under different sedation depths., Methods: A stabilized inverse probability of treatment weighting cohort study was conducted using data from the Medical Information Mart for Intensive Care IV database from 2008 to 2019. Adult intensive care unit (ICU) patients who were administered DEX or propofol as the primary sedative were identified. Various statistical methods were used to evaluate the effects of DEX versus propofol on outcomes., Results: Data on 107 and 2318 patients in DEX and propofol groups, respectively, were analyzed. Compared to the propofol group, the DEX group exhibited longer ventilator-free days on day 28 and a shorter ICU stay. Conversely, it showed null associations of DEX with the risk of 90-day ICU mortality, the odds of persistent organ dysfunction on day 14 and acute kidney injury, and the duration of vasopressor-free days on day 28. Subgroup analyses revealed that DEX positively impacted persistent organ dysfunction on day 14, ventilator-free days on day 28, and ICU stay in the subgroup with a Richmond Agitation Sedation Scale (RASS) score of ≥-2. However, DEX negatively impacted 90-day ICU mortality, persistent organ dysfunction on day 14, and ventilator-free days on day 28 in the subgroup with a RASS score of <-2., Conclusion: Our results indicated that, compared with propofol, DEX had beneficial and adverse impacts on certain ICU outcomes in critically ill patients, and these impacts appeared to depend on sedation depths., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial., Objective: This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake)., Design: A systematic review of randomised controlled trials (RCTs) with meta-analyses., Data Sources: PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024., Eligibility Criteria: RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies., Results: This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n  = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation ( P  < 0.01, I2  = 82%). No significant difference was found between different control drugs ( P  = 0.97, I2  = 82%)., Conclusion: Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Remimazolam tosilate is a new type of benzodiazepine currently used for gastrointestinal endoscopy and can be combined with alfentanil., Aim: This trial compared the effectiveness and safety of remimazolam with alfentanil to propofol with alfentanil in patients undergoing gastrointestinal endoscopy., Method: One hundred and sixty-six patients were randomly divided into propofol-alfentanil anaesthesia (Group P) and remimazolam-alfentanil anaesthesia (Group R). The primary outcomes were perioperative haemodynamic variables, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and oxygen saturation (SpO 2 ) preoperatively (T0); after anaesthesia induction (T1); when the gastroscope passed through the oropharynx (T2); 3 min (T3), 5 min (T4) and 7 min (T5) after T2; at the end of surgery (T6); and when patients successfully awakened (T7). The secondary outcomes included induction and awakening time, patient satisfaction, operator satisfaction, and adverse event occurrences., Results: Compared with those in Group P, the SBP in Group R was significantly higher at T1, T2, T3, and T6 (P < 0.05); the DBP and MAP were significantly higher at T1, T2, T3, T5, and T6 (P < 0.05); the HR was significantly faster at T1 to T6 (P < 0.05); the SpO 2 was significantly higher at T1 to T4 (P < 0.05); the incidences of hypoxemia, hypotension, and drug injection pain were significantly lower in Group R (P < 0.05); the incidence of hiccups was higher (P < 0.05); the awakening time was shorter in Group R (P < 0.05); and the operator satisfaction score was high (P < 0.05)., Conclusion: Compared to propofol with alfentanil, remimazolam with alfentanil can be used safely and effectively for sedation in patients undergoing gastrointestinal endoscopy, with less impact on the patient's circulatory and respiratory systems and a lower incidence of adverse events., Trial Registration: This trial protocol was registered in the Chinese Clinical Trial Registry (ChiCR2300077252, date: 2023-11-02)., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)