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Cureus Jul 2023Background Behavioral management techniques are employed for children who are fearful and uncooperative. Pharmacologic sedation and anesthesia are frequently utilized to...
Background Behavioral management techniques are employed for children who are fearful and uncooperative. Pharmacologic sedation and anesthesia are frequently utilized to manage pain and anxiety in pediatric dental patients. Aim To evaluate the intraoperative and postoperative pain levels during dental treatment of children sedated with 1.5 μg/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide. Materials and methods In this crossover study, 24 children between the ages of five and seven years were randomly assigned to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhaled nitrous oxide during three different visits. At each visit, a single pulp therapy procedure was conducted after administering the respective sedative agent, and the pain levels were documented. There was a one-week interval between each visit to allow for a washout period. The data were analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp, Armonk, NY, United States) using the Wilcoxon signed-rank test and Kruskal-Wallis H test (p < 0.05). Results All three sedative agents were equally effective in controlling postoperative and intraoperative pain. Although there was no statistically significant difference among the groups, clinically, midazolam showed lower intraoperative pain levels (mean 1.78 ± 1.42). Conclusion In pediatric dental patients, intranasal midazolam at a dosage of 0.3 mg/kg and intranasal dexmedetomidine at a dosage of 1.5 μg/kg demonstrate comparable effectiveness to nitrous oxide sedation in pain management. These options serve as effective alternatives for anxious children who may not tolerate nitrous oxide sedation.
PubMed: 37575859
DOI: 10.7759/cureus.41676 -
Journal of Clinical Neurophysiology :... Jul 2024To assess the clinical effectiveness of treating acute seizures with midazolam and lidocaine infusion.
PURPOSE
To assess the clinical effectiveness of treating acute seizures with midazolam and lidocaine infusion.
METHODS
This single-center historical cohort study included 39 term neonates with electrographic seizures who underwent treatment with midazolam (1st line) and lidocaine (2nd line). Therapeutic response was measured using continuous video-EEG monitoring. The EEG measurements included total s eizure burden (minutes), maximum ictal fraction (minutes/hour), and EEG-background (normal/slightly abnormal vs. abnormal). Treatment response was considered good (seizure control with midazolam infusion), intermediate (need to add lidocaine to the control), or no response. Using clinical assessments supplemented by BSID-III and/or ASQ-3 at 2 to 9 years old age, neurodevelopment was classified as normal, borderline, or abnormal.
RESULTS
A good therapeutic response was obtained in 24 neonates, an intermediate response in 15, and no response in any of the neonates. Babies with good response showed lower values in maximum ictal fraction compared with those with intermediate response (95% CI: 5.85-8.64 vs. 9.14-19.14, P = 0.002). Neurodevelopment was considered normal in 24 children, borderline in five, and abnormal in other 10 children. Abnormal neurodevelopment was significantly associated with an abnormal EEG background, maximum ictal fraction >11 minutes, and total s eizure burden >25 minutes (odds ratio 95% CI: 4.74-1708.52, P = 0.003; 1.72-200, P = 0.016; 1.72-142.86, P = 0.026, respectively) but not with the therapeutic response. Serious adverse effects were not recorded.
CONCLUSIONS
This retrospective study suggests that the midazolam/lidocaine association could potentially be efficacious in decreasing seizure burden in term neonates with acute seizures. These results would justify testing the midazolam/lidocaine combination as a first-line treatment for neonatal seizures in future clinical trials.
Topics: Humans; Midazolam; Lidocaine; Seizures; Male; Female; Infant, Newborn; Electroencephalography; Anticonvulsants; Treatment Outcome; Cohort Studies; Child, Preschool; Retrospective Studies; Drug Therapy, Combination; Infant; Child
PubMed: 37099703
DOI: 10.1097/WNP.0000000000001013 -
Frontiers in Pharmacology 2023Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on...
Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on drug-drug interactions (DDI) about vortioxetine. In this paper, the inhibitory effect of vortioxetine on cytochrome P450 (CYP450) and the type of inhibitory mechanism were investigated in human and rat liver microsomes. We set up an incubation system of 200 μL to measure the metabolism of probe substrates at the present of vortioxetine at 37°C. The concentrations of the metabolites of probe substrates were all measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. It was found no time-dependent inhibition (TDI) of vortioxetine through determination of half-maximal inhibitory concentration (IC) shift values. The enzymes and metabolites involved in this experiment in human and rats were as follows: CYP3A4/CYP3A (midazolam); CYP2B6/CYP2B (bupropion); CYP2D6/CYP2D (dextromethorphan); CYP2C8/CYP2C-1 (amodiaquine); CYP2C9/CYP2C-2 (losartan); and CYP2C19/CYP2C-3 (mephenytoin). We found that vortioxetine competitively inhibited CYP2C19 and CYP2D6 in human liver microsomes (HLMs) with inhibition constant (K) values of 2.17 μM and 9.37 μM, respectively. It was noncompetitive inhibition for CYP3A4 and CYP2C8, and its K values were 7.26 μM and 6.96 μM, respectively. For CYP2B6 and CYP2C9, vortioxetine exhibited the mixed inhibition with K values were 8.55 μM and 4.17 μM, respectively. In RLMs, the type of vortioxetine inhibition was uncompetitive for CYP3A and CYP2D (K = 4.41 and 100.9 μM). The inhibition type was competitive inhibition, including CYP2B and CYP2C-2 (K = 2.87 and 0.12 μM). The inhibition types of CYP2C-1 and CYP2C-3 (K = 39.91 and 4.23 μM) were mixed inhibition and noncompetitive inhibition, respectively. The study of the above mechanism will provide guidance for the safe clinical use of vortioxetine so that the occurrence of DDI can be avoided.
PubMed: 37790811
DOI: 10.3389/fphar.2023.1199548 -
Indian Journal of Anaesthesia Nov 2023Cancer is a leading cause of mortality worldwide. Despite advancements in cancer management, cancer progression remains a challenge, requiring the development of novel...
BACKGROUND AND AIMS
Cancer is a leading cause of mortality worldwide. Despite advancements in cancer management, cancer progression remains a challenge, requiring the development of novel therapies. Midazolam is a commonly used adjunct to anaesthesia care for various surgeries, including cancer. Recently, there has been a growing interest in exploring the potential role of midazolam as an anticancer agent; however, the exact mechanism of this linkage is yet to be investigated thoroughly.
METHODS
Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, this systematic review presented aggregated evidence (till November 2022) of the effects of midazolam on cancer progression and survival. All primary research article types where midazolam was administered or on subjects with cancers were included. No restrictions were applied on routes of administration or the type of cancer under investigation. Narrative synthesis depicted qualitative findings, whereas frequencies and percentages presented numerical data.
RESULTS
Of 1720 citations, 19 studies were included in this review. All articles were preclinical studies conducted either (58%, 11/19) or both and (42%, 8/19). The most studied cancer was lung carcinoma (21%, 4/19). There are two main findings in this review. First, midazolam delays cancer progression (89%, 17/19). Second, midazolam reduces cancer cell survival (63%, 12/19). The two major mechanisms of these properties can be explained via inducing apoptosis (63%, 12/19) and inhibiting cancer cell proliferation (53%, 10/19). In addition, midazolam demonstrated antimetastatic properties via inhibition of cancer invasion (21%, 4/19), migration (26%, 5/19), or epithelial-mesenchymal transition (5%, 1/19). These anticancer properties of midazolam were demonstrated through different pathways when midazolam was used alone or in combination with traditional cancer chemotherapeutic agents.
CONCLUSION
This systematic review highlights that midazolam has the potential to impede cancer progression and decrease cancer cell survival. Extrapolation of these results into human cancer necessitates further investigation.
PubMed: 38213688
DOI: 10.4103/ija.ija_731_23 -
Drug Design, Development and Therapy 2023Although remimazolam is a popular novel anesthetic, there is a lack of data in the literature about current and future trends. Therefore, the aim of this study was to...
PURPOSE
Although remimazolam is a popular novel anesthetic, there is a lack of data in the literature about current and future trends. Therefore, the aim of this study was to explore emerging trends and potential hotspots of remimazolam research over the past 15 years through bibliometric methods.
METHODS
Relevant articles on remimazolam published from 2007 to 2022 and propofol from 1997 to 2001 were retrieved from the Web of Science Core Collection database. Data were collected using Microsoft Excel and graphs were generated with the Bibliometrix package in R software. Visual bibliometric maps were created using VOS viewer and CiteSpace software.
RESULTS
In total, 184 articles were included for analysis. Remimazolam-related research tended to increase, especially from 2020 to 2022. China produced the most publications (327), whereas the USA dominated in quality (h-index = 16). Among institutions, PAION Deutschland GmbH produced the most articles (Np = 21). Similar to initial research and development of propofol, the hotspots of remimazolam research have extended beyond pharmacokinetics and pharmacodynamics to adverse reactions, clinical scenarios, specific populations, and compatible regimens, as confirmed by high numbers of common references and keywords.
CONCLUSION
Remimazolam research has developed rapidly over the past two years. Remimazolam can achieve faster onset and recovery, and more stable hemodynamics than midazolam or propofol, enabling gradual piloting of applications from endoscopy and general anesthesia to sedation of critical care patients; foreseeing specific population (patients with hepatic or renal impairment and reduced cardiovascular reserve, the elderly, and children) through compatible anesthetics regimens to more optimal and safe. Future studies of remimazolam are likely to include adverse reactions, effects on different organ systems, and identification of monitoring indicators.
Topics: Child; Aged; Humans; Propofol; Benzodiazepines; Anesthesia, General; Bibliometrics
PubMed: 37496748
DOI: 10.2147/DDDT.S411829 -
Molecules (Basel, Switzerland) Oct 2023CYP 3A4 and CYP 3A5 are two important members of the human cytochrome P450 family. Although their overall structures are similar, the local structures of the active site...
CYP 3A4 and CYP 3A5 are two important members of the human cytochrome P450 family. Although their overall structures are similar, the local structures of the active site are different, which directly leads to obvious individual differences in drug metabolic efficacy and toxicity. In this work, midazolam (MDZ) was selected as the probe substrate, and its interaction with two proteins, CYP 3A4 and CYP 3A5, was studied by molecular dynamics simulation (MD) along with the calculation of the binding free energy. The results show that two protein-substrate complexes have some similarities in enzyme-substrate binding; that is, in both complexes, Ser119 forms a high occupancy hydrogen bond with MDZ, which plays a key role in the stability of the interaction between MDZ and the enzymes. However, the complex formed by CYP 3A4 and MDZ is more stable, which may be attributed to the sandwich structure formed by the fluorophenyl group of the substrate with Leu216 and Leu482. Our study interprets the binding differences between two isoform-substrate complexes and reveals a structure-function relationship from the atomic perspective, which is expected to provide a theoretical basis for accurately measuring the effectiveness and toxicity of drugs for individuals in the era of precision medicine.
Topics: Humans; Midazolam; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Catalytic Domain; Protein Isoforms
PubMed: 37836743
DOI: 10.3390/molecules28196900 -
British Journal of Anaesthesia Jun 2024Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable...
BACKGROUND
Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative-hypnotics on sleep homeostasis is not clear.
METHODS
We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague-Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index.
RESULTS
Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01).
CONCLUSIONS
In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis.
Topics: Animals; Rats, Sprague-Dawley; Sevoflurane; Propofol; Dexmedetomidine; Homeostasis; Hypnotics and Sedatives; Midazolam; Male; Sleep; Rats; Electroencephalography; Anesthetics, Inhalation; Wakefulness
PubMed: 38071152
DOI: 10.1016/j.bja.2023.11.014 -
The Journal of Veterinary Medical... Feb 2024Safe sedation doses for performing minor procedures such as bronchoscopy, endoscopy, and tooth extraction for beluga whales (Delphinapterus leucas) require elucidation....
Safe sedation doses for performing minor procedures such as bronchoscopy, endoscopy, and tooth extraction for beluga whales (Delphinapterus leucas) require elucidation. This study aimed to provide suggestions for determining appropriate midazolam and butorphanol doses to adequately sedate beluga whales to complete procedures and minimize the risk of side effects. We administered midazolam and butorphanol to six captive beluga whales (9-44 years old). Topical lidocaine anesthesia was administered during bronchoscopy. The sedation doses for the beluga whales varied from 0.020 to 0.122 mg/kg for midazolam and from 0.020 to 0.061 mg/kg for butorphanol. In beluga whales, optimal midazolam and butorphanol doses were lowest in old whales. These findings contribute to knowledge regarding appropriate sedation and prevention of overdose accidents during minor procedures in beluga whales.
Topics: Animals; Beluga Whale; Butorphanol; Midazolam
PubMed: 38104973
DOI: 10.1292/jvms.23-0307 -
Forensic Toxicology Jan 2024Crime-related spiking of alcoholic drinks with prescription drugs is quite common and has been happening for centuries. This study, therefore, evaluated the effects of...
PURPOSE
Crime-related spiking of alcoholic drinks with prescription drugs is quite common and has been happening for centuries. This study, therefore, evaluated the effects of oral administration of alcohol spiked with the zolpidem and midazolam potent sedatives on inflammation, oxidative stress and various organ damage in male Swiss albino mice.
METHODS
Mice were randomly assigned into six treatment groups; the first group constituted the normal control, the second group received 50 mg/kg body weight of zolpidem only, the third group received 50 mg/kg body weight zolpidem dissolved in 5 g/kg alcohol, the fourth group received 50 mg/kg midazolam only, the fifth group received midazolam (50 mg/kg) dissolved in 5 g/kg alcohol and the sixth group received 5 g/kg alcohol.
RESULTS
Alcohol-induced significant reduction in neurological function and altered blood hematological indicators. Such neurological impairment and negative effects on blood were exacerbated in mice administered with spiked alcohol. Additionally, midazolam and zolpidem enhanced alcohol-driven elevation of liver function markers; the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) gamma glutamyltransferase (GGT), total bilirubin and alkaline phosphatase. Exposure to alcohol and/or spiked alcohol led to significant augmentation of nitric oxide and malonaldehyde, with concomitant depletion of liver glutathione (GSH) levels. Similarly, serum levels of pro-inflammatory cytokines tumor necrosis factor alpha and interferon-gamma were increased by co-exposure with midazolam or zolpidem. Alcohol-induced hepatotoxicity and nephrotoxicity were amplified by exposure to alcohol spiked with midazolam/zolpidem.
CONCLUSION
Exposure to alcohol spiked with midazolam or zolpidem appears to exacerbate neurological deficits, inflammation, oxidative stress, and organ damage.
Topics: Male; Mice; Animals; Midazolam; Zolpidem; Oxidative Stress; Ethanol; Inflammation; Glutathione; Body Weight
PubMed: 37814103
DOI: 10.1007/s11419-023-00674-w -
Journal of Clinical Imaging Science 2023This study assesses the safety and efficacy of balloon-assisted gastrostomy (BAG) compared to conventional techniques using dilators.
OBJECTIVES
This study assesses the safety and efficacy of balloon-assisted gastrostomy (BAG) compared to conventional techniques using dilators.
MATERIAL AND METHODS
A single-center retrospective review of all fluoroscopically-guided percutaneous gastrostomy tube insertions from July 2017 to September 2020 was performed. Two hundred and seventy-three patients were included in this study, with 183 patients and 90 patients in the BAG and dilator groups, respectively. Fluoroscopy time, peak radiation dose, pain management, days to interventional radiology (IR) reconsultation, and post-operative complications (major and minor) for each procedure were reviewed to evaluate for statistical differences.
RESULTS
There were shorter fluoroscopy times (5.13 min vs. 7.05 min, = 0.059) and a significantly lower radiation use (Avg = 102.13 mGy vs. 146.98 mGy, < 0.05) in the BAG group. The BAG group required significantly lower operating time (41 min vs. 48 min, < 0.01) and received lower pain management (fentanyl 75 mcg and midazolam 1.5 mg, < 0.001). The mean days to IR reconsultation for the BAG group was greater (29 days vs. 26 days, = 0.38). The overall rate of minor complications (grades 1 and 2, according to the CIRSE classification system) was higher in the dilator group (39% vs. 35% in BAG group, = 0.53). No major complications were reported in either group.
CONCLUSION
BAG is a safe and efficient technique for percutaneous gastrostomy tube placement. BAG patients required significantly lesser radiation, OR time, post-operative pain management, and recorded lower postoperative complications compared to their counterparts in gastrostomies utilizing dilators.
PubMed: 37810182
DOI: 10.25259/JCIS_55_2023