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Drug Design, Development and Therapy 2022Remimazolam (CNS7056) is a novel benzodiazepine for intravenous sedation; it has an ultra-short duration of action and was recently approved for use in procedural... (Review)
Review
Remimazolam (CNS7056) is a novel benzodiazepine for intravenous sedation; it has an ultra-short duration of action and was recently approved for use in procedural sedation and general anaesthesia. It acts on γ-aminobutyric acid type A receptors and is rapidly converted into an inactive metabolite by tissue esterase enzymes. Remimazolam has been successfully used in endoscopic inspection or surgery and general anaesthesia induction and maintenance with fast and predictable onset and recovery times, high procedure success rates, and minor respiratory and hemodynamic fluctuations and without serious drug-related adverse reactions. If needed, the effects of remimazolam can be reversed by flumazenil, which allows prompt termination of sedation. Although remimazolam has great potential for sedation in patients admitted to intensive care units, future studies are needed to evaluate its efficacy and safety in patients requiring sedation for a long period, and numerous studies are warranted to explore the optimal dose in different application scenarios. The review aimed to provide an introduction to the process of remimazolam synthesis and its current clinical uses and future clinical developments.
Topics: Humans; Hypnotics and Sedatives; Midazolam; Double-Blind Method; Benzodiazepines; Anesthetics; Anesthesia, General
PubMed: 36411859
DOI: 10.2147/DDDT.S384155 -
Journal of Oral Science Jun 2021Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is... (Review)
Review
Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is expected to be safe and effective for a wide range of patients undergoing intravenous sedation for dental procedures. The aim of this literature review was to evaluate clinical and sedation outcomes for remimazolam, including method of administration, level of sedation at the dose required, and clinical adverse events. An electronic literature search of databases was conducted, and eight articles were selected for inclusion in this review. Onset time from drug administration to optimal sedation level was faster for remimazolam (around 1.5-6.4 min) than for midazolam. Recovery time was significantly shorter for remimazolam than for midazolam and propofol. A study comparing various doses of remimazolam with midazolam found no significant difference in safety. Comparison of a remimazolam group with a propofol group showed that incidences of hypotension (13.0% vs 42.9%, respectively) and respiratory depression (1.1% vs 6.9%, respectively) were significantly lower for remimazolam. Remimazolam appears to be an ideal sedative.
Topics: Benzodiazepines; Humans; Hypnotics and Sedatives; Midazolam
PubMed: 34092775
DOI: 10.2334/josnusd.21-0051 -
Korean Journal of Anesthesiology Aug 2022Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce... (Review)
Review
Intravenous anesthetic agents such as midazolam, propofol, and ketamine are routinely used to provide anesthesia and sedation. They have been shown to effectively induce and maintain amnesia, sedation, and hypnosis in various patient groups and clinical settings. However, all anesthetic agents have the potential to cause unwanted side effects such as hemodynamic instability, respiratory depression, or slow recovery due to prolonged post-procedural sedation. Remimazolam, a recently approved benzodiazepine for general anesthesia and procedural sedation in Korea, has been successfully used for these purposes. To date, inconclusive knowledge has been obtained regarding the use of remimazolam in different patient populations and under various surgical conditions. With respect to the specific pharmacokinetic and pharmacodynamic characteristics of remimazolam, the use of remimazolam is expected to increase providing safe general anesthesia and sedation. This review aims to provide an overview of the basic and clinical pharmacology of remimazolam and to compare it with midazolam and propofol.
Topics: Anesthesia, General; Anesthetics, Intravenous; Benzodiazepines; Double-Blind Method; Humans; Hypnotics and Sedatives; Midazolam; Propofol
PubMed: 35585830
DOI: 10.4097/kja.22297 -
Physiological Research Sep 2020Midazolam is a short acting sedative with small number of adverse effects. Administered orally, it is currently the most common form of conscious sedation in children....
Midazolam is a short acting sedative with small number of adverse effects. Administered orally, it is currently the most common form of conscious sedation in children. The objective of this paper is to describe effect of midazolam administered to children during dental treatment on their vital signs, and to monitor changes in children's behavior. We described values of vital signs and behavior in 418 sedations conducted in 272 children between 1-12 years of age. To achieve the following results, we used data from 272 all first-time sedations. After administration of midazolam arterial blood pressure and blood oxygen saturation decreased by values which were not clinically significant. The heart rate increased, with values staying within the limits of physiological range. The speed of onset of midazolam's clinical effects depends on age and dose. The lower age and dose correlated with the higher behavior score. The effectiveness of midazolam treatment is 97.8 %. Unwillingness of child to receive midazolam is predictor for disruptive behavior during sedation. 1.8 % of all sedation cases showed paradoxical reactions. The administration of midazolam in dose of 0.5 mg per 1 kg of child's body weight is safe and could be recommended for dental treatment in pediatric dentistry.
Topics: Administration, Oral; Child; Child Behavior; Child, Preschool; Conscious Sedation; Dentistry; Female; Humans; Hypnotics and Sedatives; Infant; Male; Midazolam; Vital Signs
PubMed: 33094628
DOI: 10.33549/physiolres.934511 -
European Journal of Heart Failure Oct 2022Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary oedema (ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE.
METHODS AND RESULTS
A randomized, multicentre, open-label, blinded endpoint clinical trial was performed in seven Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnoea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in-hospital all-cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and the composite endpoint included 30-day mortality and SAE. Analyses were made on an intention-to-treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no significant differences in the primary endpoint (in-hospital mortality for midazolam vs. morphine 12.7% vs. 17.9%; risk ratio[RR] 0.71, 95% confidence interval [CI] 0.29-1.74; p = 0.60). SAE were less common with midazolam versus morphine (18.2% vs. 42.9%; RR 0.42, 95% CI 0.22-0.80; p = 0.007), as were the composite endpoint (23.6% vs. 44.6%; RR 0.53, 95% CI 0.30-0.92; p = 0.03).
CONCLUSION
Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group.
Topics: Humans; Adolescent; Midazolam; Morphine; Pulmonary Edema; Heart Failure; Hospital Mortality
PubMed: 35780488
DOI: 10.1002/ejhf.2602 -
Annals of Emergency Medicine Dec 2021We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation.
METHODS
We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events.
RESULTS
Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]).
CONCLUSION
In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.
Topics: Adult; Anesthetics, Dissociative; Canada; Female; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Ketamine; Male; Midazolam; Middle Aged; Psychomotor Agitation
PubMed: 34353650
DOI: 10.1016/j.annemergmed.2021.05.023 -
JAMA Network Open Aug 2022Perioperative respiratory adverse events (PRAEs) are the most common complication during pediatric anesthesia, and they may be affected by the administration of... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.
IMPORTANCE
Perioperative respiratory adverse events (PRAEs) are the most common complication during pediatric anesthesia, and they may be affected by the administration of preoperative sedatives.
OBJECTIVE
To investigate the effect of intranasal dexmedetomidine or midazolam used for premedication on the occurrence of PRAEs.
DESIGN, SETTING, AND PARTICIPANTS
This single-center, double-blind, randomized clinical trial was conducted among children aged 0 to 12 years undergoing elective tonsillectomy and adenoidectomy from October 2020 to June 2021 at Children's Hospital of Xuzhou Medical University, Xuzhou, China. Data analysis was performed from June to October 2021.
INTERVENTIONS
Children were randomly assigned to 3 groups: the midazolam group received intranasal midazolam (0.1 mg/kg), and the dexmedetomidine group received intranasal dexmedetomidine (2.0 μg/kg) for premedication. The normal saline group received intranasal 0.9% saline for control.
MAIN OUTCOMES AND MEASURES
The primary outcome was the difference in the incidence of PRAEs among the 3 groups. The secondary outcomes were the frequency of the individual PRAEs, including the incidence of such events during the induction and recovery periods, postoperative emergence delirium, postoperative pain score, sedation success rate, and heart rate values.
RESULTS
A total of 384 children (median [IQR] age, 7 [5-10] years; 227 boys [59.1%]) were enrolled and randomized; 373 data sets were available for intention-to-treat analysis (124 children in the midazolam group, 124 children in the dexmedetomidine group, and 125 children in the normal saline group). After the data were adjusted for age, sex, American Society of Anesthesiologists physical status, body mass index, obstructive sleep apnea, upper respiratory tract infection, and passive smoking, children in the midazolam group were more likely to experience PRAEs than those in the normal saline group (70 of 124 children [56.5%] vs 51 of 125 children [40.8%]; adjusted odds ratio [aOR], 1.99; 95% CI, 1.18-3.35), whereas the dexmedetomidine group had a significantly lower PRAEs incidence than the normal saline group (30 of 124 children [24.2%] vs 51 of 125 children [40.8%]; aOR, 0.45; 95% CI, 0.26-0.78). Compared with the dexmedetomidine group, the midazolam group had a higher risk of PRAEs (aOR, 4.44; 95% CI, 2.54-7.76), but no other serious clinical adverse events were observed.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, intranasal midazolam used for premedication was associated with increased incidence of PRAEs, whereas premedication with intranasal dexmedetomidine was associated with reduced incidence of PRAEs. Where clinically appropriate, anesthesiologists should consider using intranasal dexmedetomidine for sedation in children undergoing tonsillectomy and adenoidectomy.
TRIAL REGISTRATION
Chinese Clinical Trial Register Identifier: ChiCTR2000038359.
Topics: Adenoidectomy; Child; Child, Preschool; Dexmedetomidine; Humans; Male; Midazolam; Premedication; Prospective Studies; Saline Solution; Tonsillectomy
PubMed: 35943745
DOI: 10.1001/jamanetworkopen.2022.25473 -
Neurocritical Care Jun 2024Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to... (Comparative Study)
Comparative Study
BACKGROUND
Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE.
METHODS
Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021.
RESULTS
We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76-8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61-97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69-9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61-111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam.
CONCLUSIONS
Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.
Topics: Humans; Ketamine; Midazolam; Status Epilepticus; Male; Female; Infant; Retrospective Studies; Child, Preschool; Child; Infant, Newborn; Infusions, Intravenous; Adolescent
PubMed: 37783824
DOI: 10.1007/s12028-023-01859-2 -
Neuropsychopharmacology : Official... Jun 2023This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community... (Randomized Controlled Trial)
Randomized Controlled Trial
This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.
Topics: Adult; Humans; Ketamine; Pilot Projects; Borderline Personality Disorder; Midazolam; Antidepressive Agents; Double-Blind Method
PubMed: 36804489
DOI: 10.1038/s41386-023-01540-4 -
Neurologic Clinics Nov 2022Treatment of seizure clusters endeavors to prevent additional seizures and avoid progression to conditions such as prolonged seizures and status epilepticus. Rescue... (Review)
Review
Treatment of seizure clusters endeavors to prevent additional seizures and avoid progression to conditions such as prolonged seizures and status epilepticus. Rescue therapies are key components of seizure action plans (SAPs) for individuals with seizure clusters. Three rescue therapies are approved in the United States for the treatment of seizure clusters: diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Diazepam rectal gel is an effective rescue therapy for seizure clusters, though adults and adolescents may have social reservations regarding its administration. Intranasal delivery of midazolam or diazepam is a promising alternative to rectal administration because these formulations offer easy, socially acceptable administration exhibit a rapid onset, and allow for the possibility of self-administration. Off-label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous (IV) formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents.
Topics: Adult; Adolescent; Humans; Lorazepam; Midazolam; Anticonvulsants; Nasal Sprays; Seizures; Status Epilepticus; Diazepam; Benzodiazepines
PubMed: 36270699
DOI: 10.1016/j.ncl.2022.03.016