OBJECTIVE: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures.
METHODS: We included trials involving painful ED procedures in children 0-18 years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.\'s classification of \"neutral\" (p ≥ 0.05), \"favorable,\" and \"unfavorable\" (p < 0.05), supporting IN midazolam or comparator, respectively, or \"indeterminate\" (unable to judge). Where possible, we pooled results using meta-analysis. Methodologic quality of evidence was evaluated using Cochrane Collaboration\'s risk of bias tool and GRADE system.
RESULTS: We included 41 trials (n = 2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR = 7.2; 95% CI: 3.43, 15.25; 3 trials; I2 = 0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was \"neutral\" versus IN ketamine and either \"neutral\" or \"unfavorable\" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR = 1.1; 95% CI: 0.74, 1.73; 2 trials; I2 = 53%), IN ketamine (RR = 1.1; 95% CI: 0.91, 1.25; 6 trials; I2 = 0%), or IN dexmedetomidine (RR = 0.4; 95% CI: 0.17, 1.05; 3 trials; I2 = 84%). Ten trials involved laceration repair. IN midazolam was \"favorable\" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD = 0.01; 95% CI:-0.32, 0.34; 2 trials; I2 = 0%) (Fig. 3E) [64,65]. Using validated instruments, IN midazolam was \"unfavorable\" versus IN dexmedetomidine but \"favorable\" versus oral diazepam and placebo.
CONCLUSIONS: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.
UNASSIGNED: OBJECTIFS: Le midazolam intranasal (IN) est l’anxiolytique le plus courant chez les enfants du service des urgences (DE), mais les preuves des avantages sont contradictoires. Nous avons synthétisé les preuves sur l’IN midazolam pour la détresse procédurale chez les enfants subissant des procédures douloureuses d’urgence. MéTHODES: Nous avons inclus des essais impliquant des procédures douloureuses d’urgence chez les enfants de 0 à 18 ans impliquant IN midazolam. Le résultat principal était la détresse procédurale. Nous avons résumé les résultats en utilisant la classification de Tricco et coll. de « neutre » (p 0,05), « favorable », « défavorable » (p < 0,05), à l’appui du midazolam IN ou du comparateur, respectivement, ou « indéterminé » (incapable de juger). Dans la mesure du possible, nous avons regroupé les résultats en utilisant la méta-analyse. La qualité méthodologique des preuves a été évaluée à l’aide de l’outil de risque de biais de Cochrane Collaboration et du système GRADE. RéSULTATS: Nous avons inclus 41 essais (n = 2973 participants). Trente essais portaient sur l’insertion intraveineuse. L’IN midazolam était supérieur au placebo (RR = 7,2; IC à 95 % : 3,43,15,25; 3 essais; I2 = 0 %). Cependant, 56 à 90 % du groupe IN midazolam a résisté à la procédure. En se concentrant sur les trois essais qui ont utilisé des mesures validées, IN midazolam était « neutre » par rapport à IN kétamine et « neutre » ou « défavorable » par rapport à IN dexmedetomidine. Il n’y avait pas de différence dans la proportion d’enfants ayant un score de détresse satisfaisant entre IN midazolam et midazolam oral (RR = 1,1; IC à 95 % : 0,74,1,73; 2 essais; I2 = 53 %), IN kétamine (RR = 1,1; IC à 95 % : 0,91,1,25; 6 essais; I2 = 0 %) ou IN dexmedetomidine (RR = 0,4; IC à 95 % : 0,17,1,05; 3 essais; I2 = 84 %). Dix essais portaient sur la réparation de la lacération. L’IN midazolam était « favorable » par rapport au placebo, mais les deux groupes ont obtenu des résultats dans la fourchette de l’anxiété. Il n’y avait pas de différence de détresse entre le midazolam IN et le midazolam oral (SMD = 0,01; IC à 95 %:-0,32,0,34; 2 essais; I2 = 0 %) (figure 3E)64,65. À l’aide d’instruments validés, l’IN midazolam était « défavorable » par rapport à l’IN dexmedetomidine, mais « favorable » par rapport au diazépam oral et au placebo.
CONCLUSIONS: Il y a peu de preuves méthodologiques rigoureuses que l’IN midazolam est meilleur que le placebo pour l’insertion IV et la réparation de lacération. Aux doses étudiées, des preuves préliminaires suggèrent que l’IN dexmedetomidine peut être supérieure à l’IN midazolam pour l’insertion IV et la réparation de lacération.

UNASSIGNED: Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population.
UNASSIGNED: This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups.
UNASSIGNED: Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants.
UNASSIGNED: This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient\'s tolerance.

OBJECTIVE: Management of primary healthcare and routine minor procedures for children with autism spectrum disorder (ASD) can be challenging; therefore, when behavioural strategies fail, sedative medications are often employed. We evaluated the effectiveness of the current pharmacological strategies for managing children with ASD.
METHODS: We performed a systematic review and meta-analysis of the current approaches for procedural sedation in children with ASD.
RESULTS: Twenty studies met inclusion criteria. Dexmedetomidine, midazolam, propofol and chloral hydrate were the most efficient agents for successful procedures, while propofol had the highest number of adverse events. The most frequently used agents were dexmedetomidine and midazolam or a combination of the two, and the effectiveness of dexmedetomidine plus midazolam was superior to dexmedetomidine alone.
CONCLUSIONS: Multiple effective drug regimens exist for procedural sedation in children with ASD. These results could support the development of specific guidelines for procedural sedation in children with ASD.

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians\' awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.

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

UNASSIGNED: Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone.
UNASSIGNED: A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, \"Cochrane Central Register of Controlled Trials,\" Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received.
UNASSIGNED: From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating \"high concerns\" for bias.
UNASSIGNED: Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs.

Magnetic resonance imaging (MRI) is a critical diagnostic tool that often requires patient sedation to ensure optimal image quality and patient comfort, particularly in those with anxiety or an inability to remain still. This comprehensive review examines the efficacy, safety, and practical considerations of three commonly used intravenous sedatives, namely, fentanyl, butorphanol, and midazolam, in adult populations undergoing MRI procedures. This review highlights the pharmacological profiles, advantages, and limitations associated with each sedative agent through a detailed analysis of current literature, clinical guidelines, and practice-based evidence. Fentanyl is noted for its potent analgesic properties and rapid onset of action, making it suitable for painful procedures. Butorphanol, with its unique opioid agonist-antagonist activity, presents an alternative with a balance between analgesia and sedation, potentially offering a safer profile for certain patient populations. Midazolam, widely recognized for its anxiolytic and amnestic effects, remains a staple in managing procedure-related anxiety. The review further discusses patient selection criteria, dosing strategies, and the importance of individualized sedation planning to enhance patient experience and procedural outcomes. Future directions highlight the potential of emerging sedation agents and non-pharmacological approaches to improve patient comfort and compliance. The findings underscore the necessity for healthcare providers to adapt sedation practices to the specific needs of each patient, considering both the clinical context and the inherent characteristics of the sedative agents. This review aims to guide clinicians in selecting the most appropriate sedation strategy for adult patients undergoing MRI, optimizing patient care and diagnostic efficacy.

Midazolam, a short-acting benzodiazepine, is widely used to alleviate patient anxiety, enhance compliance, and aid in anesthesia. While its side effects are typically dose-dependent and manageable with vigilant perioperative monitoring, serious cardiorespiratory complications, including fatalities and permanent neurological impairment, have been documented. Prolonged exposure to benzodiazepines, such as midazolam, has been associated with neurological changes in infants. Despite attempts to employ therapeutic drug monitoring for optimal sedation dosing, its efficacy has been limited. Consequently, efforts are underway to identify alternative predictive markers to guide individualized dosing and mitigate adverse effects. Understanding these factors is crucial for determining midazolam\'s suitability for future administration, particularly after a severe adverse reaction. This article aims to elucidate the factors influencing midazolam\'s pharmacokinetics and pharmacodynamics, potentially leading to adverse events. Finally, a case study is presented to exemplify the complex investigation into the causative factors of midazolam-related adverse events.

OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of intranasal midazolam (in-MDZ) administration for antiseizure treatment in adults.
METHODS: Embase and Medline literature databases were searched. We included randomized trials and cohort studies (excluding case series) of adult patients (≥ 18 years of age) examining in-MDZ administration for epilepsy, epileptic seizures, or status epilepticus published in English between 1985 and 2022. Studies were screened for eligibility based on predefined criteria. The primary outcome was the efficacy of in-MDZ administration, and the secondary outcome was its tolerability. Extracted data included study design, patient characteristics, intervention details, and outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool.
RESULTS: A total of 12 studies with 929 individuals treated with in-MDZ were included. Most studies were retrospective, with their number increasing over time. Administered in-MDZ doses ranged from 2.5 to 20 mg per single dose. The mean proportion of successful seizure termination after first in-MDZ administration was 72.7% (standard deviation [SD] 18%), and the proportion of seizure recurrence or persistent seizures ranged from 61 to 75%. Most frequent adverse reactions to in-MDZ were dizziness (mean 23.5% [SD 38.6%]), confusion (one study; 17.4%), local irritation (mean 16.6% [SD 9.6%]), and sedation (mean 12.7% [SD 9.7%]).
CONCLUSIONS: Administration of in-MDZ seems promising for the treatment of prolonged epileptic seizures and seizure clusters in adults. Limited evidence suggests that intranasal administration is safe. Further research is warranted because of the heterogeneity of cohorts, the variation in dosages, and the lack of uniformity in defining successful seizure termination.

OBJECTIVE: This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the goal of offering comprehensive clinical evidence.
METHODS: Following predefined inclusion criteria, five databases were systematically searched, with a focus on identifying randomized controlled trials (RCTs) that compared the administration of dexmedetomidine and midazolam during complex digestive endoscopy procedures. The statistical software Stata 15.1 was employed for meticulous data analysis.
RESULTS: Sixteen RCTs were encompassed, involving a total of 1218 patients. In comparison to the midazolam group, dexmedetomidine administration was associated with a reduced risk of respiratory depression (RR=0.25, 95 %CI: 0.11-0.56) and hypoxemia (RR=0.22, 95 %CI: 0.12-0.39). Additionally, the dexmedetomidine group exhibited lower incidence rates of choking (RR=0.27, 95 %CI: 0.16-0.47), physical movement (RR=0.16, 95 %CI: 0.09-0.27), and postoperative nausea and vomiting (RR=0.56,95 %CI: 0.34-0.92). Patients and endoscopists in the dexmedetomidine group reported higher levels of satisfaction (patient satisfaction: SMD=0.73, 95 %CI: 0.26-1.21; endoscopist satisfaction: SMD=0.84, 95 %CI: 0.24-1.44). The incidence of hypotension and anesthesia recovery time did not significantly differ between the two groups (hypotension: RR=1.73,95 %CI:0.94-3.20; anesthesia recovery time: SMD=0.02, 95 %Cl: 0.44-0.49). It is noteworthy that the administration of dexmedetomidine was associated with a significant increase in the incidence of bradycardia in patients.
CONCLUSIONS: Compared to midazolam, dexmedetomidine exhibits a favorable safety profile for use in complex gastrointestinal endoscopy by significantly reducing the risk of respiratory depression and hypoxemia. Despite this, dexmedetomidine is associated with a higher incidence of bradycardia. These findings underscore the need for further research through larger, multi-center studies to thoroughly investigate dexmedetomidine\'s safety and efficacy.