Short-acting Benzodiazepine Research Articles

Anesthesia for Bronchoscopy-An Update.

The field of interventional pulmonology has grown immensely and is increasingly recognized as a subspecialty. The new procedures introduced in the last decade pose unique challenges, and anesthesiologists need to readapt to their specific demands. In this review, we extensively discuss the pathophysiology, technical aspects, preprocedural preparation, anesthetic management, and postprocedural challenges of many new procedures such as navigational bronchoscopy, endobronchial valve deployment, and bronchial thermoplasty. Majority of these procedures are performed under general anesthesia with an endotracheal tube. Total intravenous anesthesia with rocuronium as a muscle relaxant seems to be the standard US practice. The easy availability and proven safety and efficacy of sugammadex as a reversal agent of rocuronium has decreased the need for high-dose remifentanil as an agent to avoid muscle relaxants. Additional research is available with regard to the utility of nebulized lidocaine and is discussed. Finally, two newer drugs administered for conscious sedation (typically without the need of an anesthesiologist) are likely to gain popularity in the future. Remimazolam is a new short-acting benzodiazepine with a relatively faster offset of clinical effects. Dexmedetomidine, a selective adrenergic agonist, is increasingly employed in bronchoscopy as a sedative during bronchoscopic procedures.

The effect of intraoperative midazolam on postoperative delirium in older surgical patients: a prospective, multicentre cohort study.

Midazolam is a short-acting benzodiazepine frequently used in the perioperative setting. This study aimed to investigate the potential impact of intraoperative midazolam on postoperative delirium (POD) in older patients undergoing non-cardiac surgery. This study included patients aged ≥ 65 years who received general anaesthesia between April 2020 and April 2022 in multiple hospitals across China. POD occurring within 7 days was assessed using the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM). Univariable and multivariable logistic regression models based on the random effects were used to determine the association between midazolam administration and the occurrence of POD, presented as risk ratio (RR) and 95% confidence intervals (CI). Kaplan-Meier cumulative incidence curve was plotted to compare the distribution of time to POD onset between patients who received midazolam and those who did not. Subgroup analyses based on specific populations were performed to explore the relationship between midazolam and POD. In all, 5,663 patients were included, of whom 723 (12.8%) developed POD. Univariate and multivariable logistic regression analyses based on random effects of different hospitals showed no significant association between midazolam medication and POD among older population (unadjusted RR=0.96, 95% CI: 0.90-1.30, P=0.38; adjusted RR=1.09, 95% CI: 0.91-1.33, P=0.35). Kaplan-Meier curve showed no difference in the distribution of time to POD onset (Hazard ratio [HR]=1.02, 95%CI: 0.88-1.18, P=0.82). The results of subgroup analyses found that intraoperative midazolam treatment was not associated with POD in the specific subgroups of patients. Intraoperative administration of midazolam may not be associated with an increased risk of POD in older patients undergoing non-cardiac surgery.

Clinical implications of midazolam in preoperative anxiety and sedation: a review

Preoperative anxiety, a common reaction to the unfamiliar setting of medical procedures, affects 60-80% of patients and can lead to significant psychological and physiological stress. This stress can exacerbate hemodynamic instability during surgery, complicate anesthetic management, and contribute to adverse postoperative outcomes such as increased pain perception, longer recovery times, and extended hospital stays. Midazolam, a short-acting benzodiazepine, is frequently used to address these issues due to its rapid onset and effective anxiolytic and sedative properties. By acting on GABA-A receptors, midazolam provides relief from preoperative anxiety and facilitates smoother anesthesia induction. However, its use is not without risks, including potential respiratory depression, paradoxical reactions, and oversedation, which may be particularly concerning in vulnerable populations. These concerns have prompted exploration of non-pharmacological approaches, such as cognitive-behavioral therapy and mindfulness-based interventions, which can reduce anxiety without the side effects associated with pharmacological agents. This review aims to critically evaluate the clinical implications of midazolam use for preoperative anxiety and sedation, highlighting its efficacy, safety profile, and the growing interest in alternative non-pharmacological strategies.

The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review.

Existing therapeutic alternatives for neonatal crises have expanded in recent decades, but no consensus has been reached on protocols based on neonatal seizures. In particular, little is known about the use of midazolam in newborns. The aim of our study is to evaluate the response to midazolam, the appearance of side effects, and their impact on therapeutic decisions. This is a STROBE-conformed retrospective observational study of 10 patients with neonatal seizures unresponsive to common antiseizure drugs, admitted to San Marco University Hospital's neonatal intensive care (Catania, Italy) from September 2015 to October 2022. In our database search, 36 newborns were treated with midazolam, but only ten children met the selection criteria for this study. Response was assessed both clinically and electrographic. Only 4 patients at the end of the treatment showed a complete electroclinical response; they were full-term infants with a postnatal age greater than 7 days. Non-responders and partial responders are all premature (4/10) or full-term neonates who started therapy in the first days of life (< 7th day) (2/10). Neonatal seizures in preterm show a lower response rate to midazolam than seizures in full-term infants, with poorer prognosis. Liver and renal function and central nervous system development are incomplete in premature infants and the first days of life. In this study, we show that midazolam, a short-acting benzodiazepine, appears to be most effective in full-term infants and after 7 days of life.

Remimazolam-Update on basic pharmacologic principles and clinical potential

In recent years the still relatively new short-acting benzodiazepine remimazolam has been approved and clinically implemented in several countries and regions. Remimazolam is also now approved in the EU and the market launch in Germany is expected in the not too distant future. This is therefore a good point in time to summarize the current evidence for various areas of application, including general anesthesia, sedation and intensive care medicine as well as different dosing schemes.

Toward Model-Informed Precision Dosing for Remimazolam: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Remimazolam, widely used for procedural sedation and general anesthesia, is a new ultra short-acting benzodiazepine for intravenous sedation and anesthesia. We aim to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam and its metabolite CNS 7054 in healthy Chinese volunteers using population analysis and suggest an optimal dosing regimen for sedation therapy. Data were collected from a single-center, placebo-controlled, randomized, and dose-escalation clinical pharmacology study. Forty-six healthy volunteers received a single infusion dose of remimazolam, while nine healthy subjects received a continuous infusion of remimazolam. A population PK/PD model was established and RxODE and Shiny in R were used to design the remimazolam dosing regimens. A three-compartment model best described the PK of remimazolam and a two-compartment model with one transit compartment was adopted for CNS 7054. The relationship between exposure and the bispectral index was best described using an effect compartment model with an inhibitory sigmoid model. Additionally, a web-based dashboard was developed to provide individualized dosing regimens, complemented by a graphical illustration of the PK/PD profiles of the proposed dosing regimen. The established population PK/PD model characterized the dose-exposure-response relationship of remimazolam well, which could be applied to optimize individual dosing regimens.

Remimazolam anesthesia in pediatric patients undergoing cardiac catheterization for congenital heart disease: a retrospective observational study.

Benzodiazepines are used in pediatric patients with congenital heart disease (CHD) because of their mild hemodynamic depressant effects. A novel short-acting benzodiazepine, remimazolam, is expected to be suitable for these patients. We examined the characteristics of remimazolam anesthesia in pediatric patients with CHD undergoing cardiac catheterization. This single-center retrospective study included pediatric patients undergoing cardiac catheterization for CHD. The primary outcome was the remimazolam dose for loss of consciousness. Secondary outcomes included the mean maintenance remimazolam dose, recovery time from anesthesia, predicted remimazolam concentration at emergence, decrease in blood pressure and heart rate, vasopressor administration during anesthesia, electroencephalogram index (bispectral index: BIS or patient state index: PSI), and life-threatening adverse events. Thirty-nine patients, aged 2months to 16years, were included. Thirty-three patients received a median [interquartile] midazolam dose of 0.10 [0.10-0.10] mg.kg-1 in the pre-anesthesia room. The remimazolam dose for loss of consciousness was 0.34 [0.26-0.45] mg.kg-1. The mean maintenance dose was 1.0 [0.8-1.4] mg.kg-1.h-1. The recovery time was 15 [12-17] min. The predicted remimazolam concentration at emergence was 0.4-1.2µg.ml-1 in 3-6-year-old patients. Blood pressure and heart rate decreased by 30% in 15 and 6 patients, respectively. Vasopressors were administered as a bolus in 8 patients. The BIS or PSI did not fall ≤ 60 or ≤ 50, respectively, in 51% of patients before tracheal intubation. No life-threatening adverse events were reported. Remimazolam is a good alternative anesthetic agent for pediatric patients undergoing cardiac catheterization for CHD.

Use of sodium oxybate for the treatment of alcohol withdrawal syndrome in patients with acute alcohol-associated hepatitis: A 4-patient case report.

During the treatment of alcohol use disorder, alcohol withdrawal syndrome (AWS) can occur. Benzodiazepines remain the "gold standard" for the pharmacological treatment of AWS. However, other drugs have been approved in some European Countries for the treatment of AWS: namely, clomethiazole in Spain and Germany and sodium oxybate in Italy and Austria. Acute alcohol-associated hepatitis (AAH) is a distinct clinical syndrome characterized by the recent onset of jaundice with or without other signs of liver decompensation in patients with ongoing alcohol consumption. We report 4 paradigmatic clinical cases to analyze the efficacy, safety, and tolerability of the very short half-life (30-45 minutes) sodium oxybate (SO) in the management of AWS with moderate to severe AAH. Compared to SO, "as needed" short-acting benzodiazepines, currently prescribed to treat AWS in patients with AAH, have a much longer half-life (5-25 hours) which increases the risk of drug accumulation. The very short half-life of SO provides a fixed dose approach allowing for a more effective control of AWS than "as needed" therapy throughout the 24 hours. Patients reported anxiety, agitation, diffuse abdominal pain, loss of appetite, and nausea with elevation in serum bilirubin and 2 of them had abdomen distension due to ascites. Patients were affected by moderate or severe AWS and moderate or severe AAH on alcohol-related liver cirrhosis. In order to suppress AWS, all patients were treated with oral sodium oxybate at a dose of 25 mg/kg/day, progressively increased to 50 to 100 mg/kg/day, divided into 3 to 5 administrations. SO was efficient, safe and tolerable in suppressing AWS even in patients with severe AAH. All treated patients showed a rapid improvement of all symptom (via the Clinical Institute of Withdrawal Assessment for Alcohol Scale) and liver test scores (Model for End-Stage Liver Disease). Because of its short half-life, SO can be considered a safe and effective pharmacological option for the AWS in patients with moderate to severe AAH even in comparison to short-acting benzodiazepines, thus avoiding the risk of accumulation. Notably, SO guarantees a fixed approach to cover the possible onset of AWS throughout the 24 hours.

The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy

BackgroundThe main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition.MethodsA randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People’s Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital.ResultsThe successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. Conclusions: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal.Trial registrationChina Clinical Trial Center with registration number: 2100052615,02/11/2021.

Incompatibility of the short-acting benzodiazepine remimazolam with common perioperative medication

BackgroundRemimazolam is a relatively new benzodiazepine with growing use in procedural sedation and general anaesthesia. Initiated by case reports, the physical incompatibility of remimazolam with ringer’s acetated and ringer’s lactated solution has been reported. More recently, remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam, have been investigated and suggested safe for coadministration with remimazolam. Apart from case reports, incompatibility for other frequently used drugs remains unknown.MethodsSixty-five drugs and intravenous fluids were tested for possible precipitation with remimazolam in a simulated y-site administration. Equal volumes of the test drug were injected into the remimazolam solution, examined and photo documented at 1, 15, 30 and 60 min after mixture. Examination was taken by two independent investigators. pH was measured before, and 60 min after mixing the drugs.ResultsSeventeen (26.15%) drugs or fluids showed precipitation, 47 (72.31%) did not show any sign of interaction. Propofol could not be assessed, because of the turbidity of the substance itself. Precipitation occurred immediately and remained stable in all timestamps. The incompatible drug-remimazolam-mixtures had a median pH of 7.15 (6.67, 8.01), the non-precipitating mixtures a median pH of 4.75 (3.8, 5.6). The pH-values of both groups were significantly different (Mann-Whitney-U-test; p < .00001). There is an increasing risk for precipitation with more basic baseline pH-levels of the tested drug. No interaction was seen in baseline pH below 5.ConclusionsRemimazolam (Byfavo®) is incompatible with ampicillin/ sulbactam, calcium gluconate, clindamycin, dexamethasone, dimenhydrinate, an 148mval/l electrolyte - glucose 1% solution (E148G1®), furosemide, a 4% gelatine volume expander (gelafundin®), heparin sodium, insulin, meropenem, sodium bicarbonate 8.4%, prednisolone, the crystalloid infusions jonosteril® and sterofundin®, thiopental and tranexamic acid. The results strongly affirm remimazolam’s safety requirements: A separate line for remimazolam and an approved compatible baseline infusion is mandatory and an alternative way to administer bolus medication is required.

Etomidate Combined with Propofol versus Remimazolam for Sedation in Elderly Patients During Gastrointestinal Endoscopy: A Randomized Prospective Clinical Trial.

Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3μg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients' Mini-cog score and recovery questionnaires were compared. Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient's life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.

Effect of remimazolam versus propofol anesthesia on postoperative delirium in neurovascular surgery: study protocol for a randomized controlled, non-inferiority trial

BackgroundRemimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the neurosurgical population due to its rapid emergence, enabling early neurological assessment, and its ability to maintain perfusion pressure, which is crucial for preventing cerebral ischemia. However, the use of benzodiazepine has been associated with an increased risk of postoperative delirium (POD). There is currently limited evidence about the relationship between remimazolam-based total intravenous anesthesia (TIVA) and POD.MethodsIn this double-blind, randomized, non-inferiority trial, we plan to include 696 adult patients with American Society of Anesthesiologists physical status class I to III, undergoing elective neurovascular surgery under general anesthesia. After informed consent, the patients will be randomized to receive either remimazolam or propofol-based TIVA with a 1:1 ratio. The primary outcome is the incidence of POD within 5 days after surgery. Secondary outcomes include subtypes, number of positive assessments and severity of POD, emergence agitation, intraoperative awareness and undesirable patient movement, intraoperative hypotension, and postoperative cognitive function. The data will be analyzed in modified intention to treat.DiscussionThis trial will evaluate the effect of remimazolam on the development of POD compared to propofol anesthesia. The results of this trial will provide evidence regarding the choice of optimal anesthetics to minimize the risk of POD in neurosurgical patients.Trial registrationThe study protocol was prospectively registered at the Clinical trials (https://clinicaltrials.gov, NCT06115031, principal investigator: Jiseon Jeong; date of first registration: November 2, 2023, before the recruitment of the first participant.

ED50 and ED95 of Remimazolam Tosilate Combined with Different Doses of Fentanyl in Elderly Patients for Painless Gastroscopy.

The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy. Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate. The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups. The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.

Advances in The Assessment of the Sedative Effect of Remimazolam

Purpose of Review: Remimazolam is a new short-acting benzodiazepine in the final stages of clinical development. The methods of monitoring sedation and assessing the depth of anesthesia for benzodiazepine sedative drugs have been fraught with controversy in clinical work. As a newly released short-acting anesthetic sedative drug that can be continuously pumped, appropriate anesthetic monitoring and sedation depth assessment tools can better help anesthesiologists make clinical decisions and reduce the emergence of perioperative complications in patients. Recent Findings: Clinical trials of remimazolam have been completed at home and abroad in various phases, and much progress has been made, but the effective sedation monitoring means of remimazolam are still not conclusive. Summary: Remimazolam has a rapid onset of action and a high rate of metabolism in the body; tissue accumulation and delayed awakening are rare. At the same time, it can be safely applied to elderly patients with a low cardiopulmonary function inhibition rate, accurate anesthesia effect, and satisfactory quality of awakening. By comparing various methods of sedation depth monitoring, the data correlation is high, which can be of significant importance for remimazolam sedation depth monitoring.

Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example.

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.

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles.

Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the perioperative phase, when patients' anxiety levels are already high. Remimazolam has replaced certain commonly used intravenous (IV) anesthetics due to its excellent safety profile, rapid onset of action, and short half-life. The four classes of BZDs, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolobenzodiazepines, and 7-nitro-benzodiazepines based on chemical structure, provide various levels of drowsiness, forgetfulness, and anxiolysis. Based on their elimination half-life, short-acting BZDs typically have a half-life ranging from one to 12 hours, e.g., oxazepam; intermediate-acting BZDs have an average elimination half-life of 12 to 40 hours, e.g., alprazolam; and long-acting BZDs have an average elimination half-life of more than 40 hours, e.g., diazepam. The chloride ion channel is conformationally shifted by the benzodiazepine molecule resulting in central nervous system (CNS) inhibition and hyperpolarization. Each type of benzodiazepine has a favored use. For example, diazepam is used to treat anxiety. Midazolam is used for its anxiolytic and anterograde amnestic effects during the perioperative phase. Anxiety and epilepsy are two conditions that lorazepam effectively treats. There are now phase II and III clinical studies investigating remimazolam. It is not sensitive to alterations in its surroundings and has a brief half-life so that it may be removed rapidly, even after extensive infusion. Being a soft drug means the body easily breaks it down via metabolism, which explains many features. Remimazolam is hydrolyzed into methanol and its carboxylic acid metabolite CNS 7054 by esterase metabolism. Therefore, remimazolam has a shorter onset time and faster recovery than other BZDs. Remimazolam is metabolized independently of any particular organ. Patients with hepatic and renal problems will not see any changes in metabolism or excretion since the drug's ester moiety makes it a substrate for general tissue esterase enzymes. Like its predecessor, midazolam, it has a high potential for addiction. Some side effects that could occur during infusion include headaches and drowsiness. In clinical trials, hypotension, respiratory depression, and bradycardia were noted in participants. BZDs are helpful when used in conjunction with anesthesia. Remimazolam stands out, thanks to its unique pharmacokinetics, pharmacodynamics, safety profile, and potential medical applications. Its desirable properties make it a potential surgical premedication and sedative in the critical care unit. Anesthesiologists and other doctors could have access to more consistent and safer medication. However, additionalcomprehensive clinical trials are necessary to understand remimazolam's advantages and disadvantages.

Predicted effect-site concentrations of remimazolam for i-gel insertion: a prospective randomized controlled study.

This study is the first to report 50% and 95% effect-site concentrations (EC50 and EC95, respectively) of the new short-acting benzodiazepine, remimazolam, for the successful insertion of i-gels with co-administration of fentanyl. Thirty patients (38 ± 5 years old, male/female = 4/26) were randomly assigned into five groups to receive one of five different remimazolam doses (0.1, 0.15, 0.2, 0.25, and 0.3mg/kg bolus followed by infusion of 1, 1.5, 2, 2.5, and 3mg/kg/h, respectively, for 10min), which were designed to maintain a constant effect-site concentration of remimazolam at the time of i-gel insertion. At 6min after the start of remimazolam infusion, all patients received 2µg/kg fentanyl. i-gel insertion was attempted at 10min and the success or failure of insertion were assessed by the patient response. Probit analysis was used to estimate the EC50 and EC95 values of remimazolam with 95% confidence intervals (CIs). In the five remimazolam dose groups, two, two, four, five, and six of the six patients in each group had an i-gel successfully inserted. Two patients in the lowest remimazolam dose group were conscious at the time of i-gel insertion and were counted as failures. The EC50 and EC95 values of remimazolam were 0.88 (95% CI, 0.65-1.11) and 1.57 (95% CI, 1.09-2.05) µg/ml, respectively. An effect-site concentration of ≥ 1.57µg/ml was needed to insert an i-gel using remimazolam anesthesia, even with 2µg/kg fentanyl. Trial registration: The study was registered in Japan Registry of Clinical Trials on 19 April 2021, Code jRCTs041210009.

Evaluation and management of insomnia in the clinical practice in Italy: a 2023 update from the Insomnia Expert Consensus Group.

Insomnia is the most reported sleep disorder in industrialized countries, affecting, in the chronic form, around 10% of the European population. In Italy, such a percentage seems to be even higher. Although insomnia can be an independent disorder, it is frequently described as comorbid condition and may precipitate, exacerbate, or prolong a broad range of physical and mental disorders. Evaluating and targeting insomnia in the Italian clinical practice should be a priority. The present expert opinions and recommendations represent an update from 2020 and insights from Insomnia Expert Consensus Group, based on systematic reviews according to PRISMA on available options in Italy from January 2020 to March 2023. We evaluated 28 papers among international guidelines, expert opinions, systematic reviews, and meta-analysis produced during the last 26months. Our findings suggest that symptoms of insomnia must be assessed in the Italian clinical practice by evaluating nocturnal and daytime symptoms, comorbid conditions, and lifestyle. Cognitive behavioral therapy for insomnia should be the first option according to availability. The choice of the drug should be based on different factors including type of insomnia, age, comorbidities, and potential side effects. If the choice would be a Z-drug or a short-acting benzodiazepine (in subjects < 65years old), the use should be in the short term (≤ 4weeks). Indeed, eszopiclone, as a new option in Italy, may present a different profile and may be used for up to 6months, also in the elderly. If the choice is melatonin, it should be used melatonin 2mg prolonged release in adults ≥ 55years for up to 13weeks. A new dual orexin antagonist, daridorexant, is available in Italy; it has been shown to be effective in adults and elderly and it can be used for at least 3months and up to 1 year.

P119: The Valladolid Multicenter Study: The Use of Benzodiacepines in the Elderly and Falls Reported By a Liaison Psychiatry Units

Objective:The objective of this study is to describe the prevalence of benzodiazepine in a sample of patients (≥65 years) attended by liaison psychiatry units (LPU) in Spain and its possible relation to falls.Methods:This is an observational., cross-sectional, multicenter study. We obtained data from a sample of 165 patients (≥65 years) admitted to 7 general hospitals in Spain referred from different departments to each liaison psychiatry unit. Data was collected for a month and a half period. Psychiatric evaluations were performed while the patients were on wards.Results:We obtained a sample of 165 patients (78 women, 88 men) with a mean age of 76,03 years old (42.10% &lt;75 years, 57,83% ≥ 75 years). Most of them were married and they lived accompanied (67,27%). Only 5,45% lived in a nursing home. 65,45% of patients had prescribed at least one psychotropic drug before LPU intervention; mainly (50,9%) benzodiazepines (60%women/40%men). 70,9% of these group of patients had more than one psychotropic drug prescribed before LPU. After LPU intervention in 39,39% at least one drug was withdrawn (in 50,81 % of cases benzodiazepines). Falls in the past 6 months were reported in 24.8% of total patients. Patients under benzodiazepine treatment had fallen in 29% of cases. After LPU intervention benzodiazepines were withdrawn in 56,25% % of them.Conclusions:Benzodiazepines are widely used in our sample and frequently is associated with polypharmacy. LPU intervention might be a useful tool to reduce the use of them, specially for those who reported falls.Longitudinal studies might be carried out to study these factors and their possible relationship with falls, given that Benzodiazepines are consistently associated with a higher risk of falls. It is unclear whether specific subgroups such as short-acting benzodiazepines and selective serotonin reuptake inhibitors are safer in terms of fall risk. Ppropriate prescription of medications such as BZDs is an important public health issue.

Anesthetic management with remimazolam in very elderly patients undergoing hybrid surgery of transcatheter aortic valve implantation plus off-pump coronary artery bypass grafting: report of two cases

BackgroundRemimazolam is a short-acting benzodiazepine with small circulatory depression. We used remimazolam for general anesthesia management in two very elderly patients undergoing hybrid surgery of transcatheter aortic valve implantation (TAVI) plus off-pump coronary artery bypass grafting (OPCABG).Case presentationA 96-year-old man (case 1) and a 92-year-old woman (case 2) had complex coronary artery disease (CAD) and severe aortic stenosis (AS) and were scheduled for TAVI plus OPCAB. Anesthesia in both patients was induced with 6 mg/kg/h remimazolam and fentanyl and maintained with 0.3 mg/kg/h and 0.5 mg/kg/h remimazolam and fentanyl, respectively. Although catecholamines were required, we successfully maintained circulation during the induction of anesthesia and the procedures of OPCAB and TAVI. Both patients were discharged without complications.ConclusionRemimazolam can be a useful option for safe general anesthesia in very elderly patients when performing hybrid surgery.