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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 -
BMC Anesthesiology Oct 2023Moderate to deep sedation is required for dental treatment of children with dental anxiety. Midazolam is the most commonly used sedative, whereas intranasal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Moderate to deep sedation is required for dental treatment of children with dental anxiety. Midazolam is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric sedation.
OBJECTIVE
The aim of this trial was to compare the sedative efficacy of oral midazolam alone with that of intranasal dexmedetomidine plus oral midazolam during dental treatment of children with dental anxiety.
DESIGN
In total, 83 children (aged 3-12 years) scheduled to undergo dental sedation were randomized to receive oral midazolam (0.5 mg/kg) and intranasal placebo, or oral midazolam (0.5 mg/kg) plus intranasal dexmedetomidine (2 µg/kg). The primary outcome was the rate of successful sedation for dental treatment. Secondary outcomes were the onset time and adverse events during and after treatment. Data analyses involved descriptive statistics and nonparametric tests.
RESULTS
The rate of successful sedation was significantly higher in combination group (P = 0.007), although the sedation onset time was significantly longer in combination group (17.5 ± 2.4 min) than in monotherapy group (15.7 ± 1.8) (P = 0.003). No children required medical intervention or oxygen therapy for hemodynamic disturbances, and the incidences of adverse events had no significant difference between groups (P = 0.660).
CONCLUSION
Combined treatment with oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (2 µg/kg) is more significantly effective for managing the behavior of non-cooperative children during dental treatment, compared to oral midazolam (0.5 mg/kg) alone. (Chinese Clinical Trial Registry: ChiCTR2100042300) TRIAL REGISTRATION: ChiCTR2100042300, Clinical trial first registration date: 17/01/2021.
Topics: Child; Humans; Midazolam; Dexmedetomidine; Outpatients; Hypnotics and Sedatives; Anesthesia; Administration, Intranasal
PubMed: 37817075
DOI: 10.1186/s12871-023-02289-5 -
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 -
Journal of the American Dental... Nov 2023Sedation with continuous dexmedetomidine and bolus midazolam administration provides a lower incidence of unacceptable patient movement during procedures but requires a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sedation with continuous dexmedetomidine and bolus midazolam administration provides a lower incidence of unacceptable patient movement during procedures but requires a longer recovery time. The authors aimed to compare recovery time and unacceptable patient movement during sedation with initial loading of dexmedetomidine followed by continuous propofol infusion with those during sedation with continuous dexmedetomidine and bolus midazolam administration.
METHODS
In this prospective randomized controlled trial, 54 patients undergoing dental surgery and requiring intravenous sedation were assigned to either the dexmedetomidine and propofol group (n = 27, dexmedetomidine administered at 6 μg/kg/h for 5 minutes, followed by continuous propofol infusion using a target-controlled infusion) or the dexmedetomidine and midazolam group (n = 27, dexmedetomidine administered at 0.2-0.7 μg/kg/h continuously after the same initial loading dose with bolus midazolam). A bispectral index of 70 through 80 was maintained during the procedure. Patient movement that interfered with the procedure and time from the end of sedation to achieving a negative Romberg sign were assessed.
RESULTS
Times from the end of sedation to achieving a negative Romberg sign in the dexmedetomidine and propofol group (median, 14 minutes [interquartile range, 12-15 minutes]) were significantly shorter (P < .001) than in the dexmedetomidine and midazolam group (median, 22 minutes [interquartile range, 17.5-30.5 minutes]). The incidence of unacceptable patient movement was comparable between groups (n = 3 in the dexmedetomidine and propofol group, n = 4 in the dexmedetomidine and midazolam group; P = .999).
CONCLUSIONS
Sedation with a single loading dose of dexmedetomidine followed by continuous propofol infusion can prevent delayed recovery without increasing unacceptable patient movement.
PRACTICAL IMPLICATIONS
The combination of dexmedetomidine and propofol may provide high-quality sedation for ambulatory dental practice. This clinical trial was registered in the University Hospital Medical Information Network Clinical Trials Registry. The registration number is UMIN000039668.
Topics: Humans; Propofol; Midazolam; Hypnotics and Sedatives; Dexmedetomidine; Prospective Studies; Conscious Sedation
PubMed: 37725033
DOI: 10.1016/j.adaj.2023.08.003 -
Paediatric Anaesthesia Nov 2023Preoperative anxiety in pediatric patients can worsen postoperative outcomes and delay discharge. Drugs aimed at reducing preoperative anxiety and facilitating... (Randomized Controlled Trial)
Randomized Controlled Trial
Postoperative recovery in preschool-aged children: A secondary analysis of a randomized controlled trial comparing premedication with midazolam, clonidine, and dexmedetomidine.
BACKGROUND
Preoperative anxiety in pediatric patients can worsen postoperative outcomes and delay discharge. Drugs aimed at reducing preoperative anxiety and facilitating postoperative recovery are available; however, their effects on postoperative recovery from propofol-remifentanil anesthesia have not been studied in preschool-aged children. Thus, we aimed to investigate the effects of three sedative premedications on postoperative recovery from total intravenous anesthesia in children aged 2-6 years.
METHODS
In this prespecified secondary analysis of a double-blinded randomized trial, 90 children scheduled for ear, nose, and throat surgery were randomized (1:1:1) to receive sedative premedication: oral midazolam 0.5 mg/kg, oral clonidine 4 μg/kg, or intranasal dexmedetomidine 2 μg/kg. Using validated instruments, outcome measures including time for readiness to discharge from the postoperative care unit, postoperative sedation, emergence delirium, anxiety, pain, and nausea/vomiting were measured.
RESULTS
After excluding eight children due to drug refusal or deviation from the protocol, 82 children were included in this study. No differences were found between the groups in terms of median time [interquartile range] to readiness for discharge (midazolam, 90 min [48]; clonidine, 80 min [46]; dexmedetomidine 100.5 min [42]). Compared to the midazolam group, logistic regression with a mixed model and repeated measures approach found no differences in sedation, less emergence delirium, and less pain in the dexmedetomidine group, and less anxiety in both clonidine and dexmedetomidine groups.
CONCLUSIONS
No statistical difference was observed in the postoperative recovery times between the premedication regimens. Compared with midazolam, dexmedetomidine was favorable in reducing both emergence delirium and pain in the postoperative care unit, and both clonidine and dexmedetomidine reduced anxiety in the postoperative care unit. Our results indicated that premedication with α -agonists had a better recovery profile than short-acting benzodiazepines; although the overall recovery time in the postoperative care unit was not affected.
Topics: Child; Humans; Child, Preschool; Midazolam; Clonidine; Dexmedetomidine; Emergence Delirium; Double-Blind Method; Hypnotics and Sedatives; Premedication; Adrenergic alpha-2 Receptor Agonists; Anesthesia, General; Pain
PubMed: 37528645
DOI: 10.1111/pan.14740 -
Journal of Pediatric Ophthalmology and... 2023To evaluate the effects of intranasal dexmedetomidine and midazolam-ketamine combination for premedication on sedation quality, oculocardiac reflex development, mask...
PURPOSE
To evaluate the effects of intranasal dexmedetomidine and midazolam-ketamine combination for premedication on sedation quality, oculocardiac reflex development, mask tolerance, and separation from parents in children who would undergo strabismus surgery.
METHODS
A total of 74 patients aged 2 to 11 years, were divided into two groups. The dexmedetomidine group (n = 37) received 1 mcg/kg of dexmedetomidine and the midalozam-ketamine group (n = 37) received 0.1 mg/kg of midazolam and 7.5 mg/kg of ketamine combination intranasally. Mean arterial pressure, peripheral oxygen saturation, Ramsay Sedation Scale values, and heart rate were recorded before and after the premedication. The children's separation from the family scores were evaluated and recorded. The mask compliance was evaluated and recorded. Patients who developed oculocardiac reflex and were administered atropine were recorded. In the postoperative period, nausea and vomiting, recovery times, and postoperative agitation were evaluated.
RESULTS
Ramsay Sedation Scale scores, mask acceptance, and family separation scores were similar in both groups ( > .05). Oculocardiac reflex was observed more in the dexmedetomidine group ( = .048). Atro-pine requirement and postoperative nausea and vomiting rates were similar in both groups ( > .05). Mean arterial pressures and heart rates were significantly lower in the dexmedetomidine group during the pre-medication period. The recovery time was longer in the midazolam-ketamine group ( < .001). The incidence of postoperative agitation was significantly lower in the midazolam-ketamine group ( = .001).
CONCLUSIONS
The sedation efficacy of intranasal dexmedetomidine and midazolam-ketamine combination that were given in premedication was similar. Oculocardiac reflex was observed more with dexmedetomidine. The recovery time was prolonged in the midazolam-ketamine group, but postoperative agitation was observed less. .
Topics: Child; Humans; Midazolam; Ketamine; Dexmedetomidine; Hypnotics and Sedatives; Premedication; Strabismus
PubMed: 36803239
DOI: 10.3928/01913913-20221219-01 -
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 -
Brain and Behavior Aug 2023Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients undergoing noncardiac surgery remains controversial.
METHODS
The final search took place on June 10, 2023. Randomized controlled trials including ketamine, ulinastatin, dexmedetomidine, parecoxib, and midazolam on the prevention and treatment of POCD in elderly undergoing noncardiac surgery were collected. A Bayesian network meta-analysis was performed to quantitatively combine the evidence.
RESULTS
A total of 35 randomized trials were finally included in this systematic review, and the overall risk of bias is Allocation concealment. These anesthetic adjuvant drugs did not show significant differences in preventing POCD on postoperative days 1 and 7 compared with each other, but ulinastatin may be more effective in preventing POCD than dexmedetomidine [odds ratio (OR) = 0.28, 95% confidence interval (CI) = (0.10, 0.71)] and parecoxib [OR = 0.3, 95% CI = (0.10, 0.82 on postoperative day 3. The efficiency ranking results also find that ulinastatin and ketamine might provide better effects regarding POCD prevention.
CONCLUSIONS
Ketamine and ulinastatin might have better effects in preventing POCD in elderly patients undergoing noncardiac surgery. Our meta-analysis provided evidence for the use of ulinastatin and ketamine in the prevention of POCD in elderly patients undergoing noncardiac surgery.
Topics: Humans; Aged; Postoperative Cognitive Complications; Postoperative Complications; Ketamine; Dexmedetomidine; Adjuvants, Anesthesia; Bayes Theorem; Network Meta-Analysis; Anesthetics; Cognitive Dysfunction
PubMed: 37431799
DOI: 10.1002/brb3.3149 -
Journal of Zoo and Wildlife Medicine :... Mar 2024Sedation, recovery response, and physiologic outcomes were evaluated in five captive reindeer () in Minnesota using a completely reversible immobilization protocol....
Sedation, recovery response, and physiologic outcomes were evaluated in five captive reindeer () in Minnesota using a completely reversible immobilization protocol. Reindeer were immobilized with butorphanol (0.23-0.32 mg/kg), midazolam (0.23-0.32 mg/kg), and medetomidine (0.15 mg/kg) (BMM) via IM dart. Induction time (IT), recumbency time (DT), and recovery time (RT) were recorded. Temperature (T), respiratory rate (RR), pulse rate (PR), pulse oximetry (SpO), arterial blood gas values including oxygen (PaO), and carbon dioxide (PaCO) tensions and lactate (Lac) were recorded preoxygen supplementation and 15 min postoxygen supplementation. Reversal was done using naltrexone (2.3-3.0 mg/kg), flumazenil (0.008-0.01 mg/kg) and atipamezole (0.62-0.78 mg/kg) (NFA) IM, limiting recumbency to 1 h. Median IT, DT, and RT were 5 min, 46 min, and 7 min, respectively. SpO (92 to 99%, = 0.125), PaO (45.5 to 97 mmHg, = 0.25), and PaCO (46.5 to 54.6 mmHg, = 0.25) all increased, whereas Lac (3.02 to 1.93 mmol/L, = 0.25) decreased between baseline and 15 min postoxygen supplementation, without statistical significance. BMM immobilization, and reversal with NFA provided rapid and effective immobilization and recovery, respectively. Oxygen supplementation mitigated hypoxemia in all reindeer.
Topics: Animals; Medetomidine; Midazolam; Butorphanol; Reindeer; Hypnotics and Sedatives; Ketamine; Oxygen; Immobilization; Heart Rate
PubMed: 38453504
DOI: 10.1638/2023-0011 -
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