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Brazilian Journal of Anesthesiology... 2023Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with oral midazolam alone for pediatric preanesthetic medication.
METHODS
The study protocol was registered in PROSPERO as CRD42020172920. A systematic literature search was conducted using Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing oral combinations of midazolam and ketamine with midazolam alone as preanesthetic medication in elective surgical pediatric patients. Meta-analyses included the following outcomes: anxiety and sedation levels, child...s behavior during separation from parents, face mask acceptance, and venipuncture. The quality of evidence was assessed using GRADE criteria.
RESULTS
Twenty studies were included. The following effects (RR (95% CI)) were observed for combinations of ketamine and midazolam relative midazolam alone: anxiolysis (1.2 (0.94...1.52); p.ß=.ß0.15; I2.ß=.ß80%; GRADE.ß=.ßvery low); satisfactory sedation (1.2 ( 1.10...1.31); p.ß<.ß0.001; I2.ß=.ß71%; GRADE.ß=.ßvery low); behavior during parental separation (1.2 (1.06...1.36); p.ß=.ß0.003; I2.ß=.ß88%; GRADE.ß=.ßvery low); facial mask acceptance (1.13 (1.04...1.24); p.ß=.ß0.007; I2.ß=.ß49%; GRADE.ß=.ßvery low); behavior during venipuncture (1.32 (1.11...1.57); p.ß=.ß0.002; I2.ß=.ß66%; GRADE.ß=.ßvery low).
CONCLUSIONS
While similar probabilities of obtaining anxiolysis were found, adequate sedation, calm behavior during child...s separation from parents, low levels of fear during face mask adaptation, and cooperative behavior during peripheral venous cannulation were more likely with midazolam-ketamine combinations.
Topics: Child; Humans; Midazolam; Ketamine; Preanesthetic Medication; Anxiety; Anesthesia; Hypnotics and Sedatives
PubMed: 34411631
DOI: 10.1016/j.bjane.2021.07.026 -
Cureus Jan 2023Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic... (Review)
Review
Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and clinical trials have shown that midazolam nasal spray could become an effective and promising alternative to conventional routes (intravenous {IV}/rectal). Therefore, we thought of conducting a systematic review and meta-analysis of midazolam (MDZ) to assess its potential outcomes. The analysis was also evaluated based on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of midazolam nasal spray. A systematic literature search was carried out through various databases to identify studies of accounted outcomes of midazolam nasal spray (MDZ-NS). Randomized and other studies of patients (12 years or older) with seizure clusters (SCs) were included. A total of three full-text articles were considered for systematic review and meta-analysis as per the inclusion and exclusion criteria. The 5 mg MDZ-NS was observed to be equally safe as a placebo, and the risk ratio (RR) was 1.01 (95% confidence interval (CI): 0.67-1.53). After the administration of MDZ-NS, either the patients remained seizure-free for six hours or more or the seizure was terminated within 10 minutes and had no recurrence between 10 minutes and six hours. The risk ratio (RR) obtained was 1.54 (95% CI: 1.25-1.91). The result was statistically significant as a higher success rate was observed with the use of 5 mg midazolam nasal spray compared to placebo (p < 0.0001). Heterogeneity was not observed in the results of the included studies (inconsistency index {I}: 0%). The present systematic review and meta-analysis demonstrated that 5 mg midazolam nasal spray was efficacious in treating patients with seizure clusters and is well-tolerated. Also, its use is relatively safe.
PubMed: 36843713
DOI: 10.7759/cureus.34064 -
Frontiers in Medicine 2021The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of remimazolam in clinical endoscopic procedure sedation. The authors...
The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of remimazolam in clinical endoscopic procedure sedation. The authors searched the databases of PubMed, Embase, and Cochrane Library for studies published until January 2, 2021, that reported remimazolam sedation for endoscopic procedures. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Cochrane Review Manager Software 5.3 was used to perform the statistical analyses. Seven relevant studies involving a total of 1,996 patients were identified. We conducted a meta-analysis of the different controls used in the studies, that is, the placebo, midazolam, and propofol. The results demonstrated that remimazolam had a strong sedative effect, and its sedative efficiency was significantly higher than that of placebo [OR = 0.01, 95% CI: (0.00, 0.10), = 30%, <0.00001]. The sedative efficiency of remimazolam was significantly higher than that of midazolam [OR = 0.12, 95% CI: (0.08, 0.21), = 0%, < 0.00001] but lesser than that of propofol [OR = 12.22, 95% CI: (1.58, 94.47), = 0%, = 0.02]. Regarding the adverse events, remimazolam is associated with a lower incidence of hypotension than placebo and midazolam. Similarly, remimazolam was associated with a lower incidence of hypotension and hypoxemia than propofol. Remimazolam is a safe and effective sedative for patients undergoing endoscopic procedures. The sedative efficiency of remimazolam was significantly higher than that of midazolam but slightly lower than that of propofol. However, the respiration and circulation inhibitory effects of remimazolam were weaker than those of midazolam and propofol.
PubMed: 34381792
DOI: 10.3389/fmed.2021.655042 -
Health Technology Assessment... Mar 2022Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded...
BACKGROUND
Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting.
OBJECTIVES
To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.
DATA SOURCES
We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020.
REVIEW METHODS
Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively.
RESULTS
Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness.
LIMITATIONS
The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.
CONCLUSIONS
Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020201953.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in ; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.
Topics: Adult; Anticonvulsants; Emergency Service, Hospital; Hospitals; Humans; Retrospective Studies; Status Epilepticus
PubMed: 35333156
DOI: 10.3310/RSVK2062 -
Cureus Aug 2022Children are particularly terrified of having dental treatment. They are physically resistant, frail, and unwilling to cooperate. This severe distress during the... (Review)
Review
Children are particularly terrified of having dental treatment. They are physically resistant, frail, and unwilling to cooperate. This severe distress during the pre-operative phase could cause the dentist to have issues with behavior control. Additionally, it may make pediatric dental treatments less effective. In order to reduce anxiety and control behavior in children receiving dental care, sedation is a pharmacological management technique that supports the provision of effective and high-quality dental services. The aim is to compare and evaluate the efficacy of sedative agents like dexmedetomidine and midazolam in pediatric dental practice. A thorough review of the literature was conducted using electronic databases like "MEDLINE, PubMed, and CENTRAL (Cochrane Central Register of Controlled Trials), as well as the World Health Organization International Clinical Trials Registry Platform, www.clinicaltrials.gov, conference proceedings abstracts, a bibliography of pertinent references, and manual searches of journals, conferences, and books". There were no restrictions on the language or the date of publication when searching the electronic databases. Randomized controlled trials were included which compared dexmedetomidine and midazolam in children up to 16 years of age subjected to dental treatment. Information on procedures, participants, interventions, outcome measures, and results were independently extracted by three review writers (TS, SL, and RO). Trial authors were contacted for papers that were confusing or lacking information. The risk of bias was evaluated for each study. We adhered to the Cochrane statistical recommendations. Three trials totaling 229 participants were included. All three studies were rated as having a low risk of bias, with none of them having a high or unclear risk. Meta-analysis was done for the available data for the primary outcomes like sedation level and recovery time. We searched for randomized controlled trials up to Jan 31, 2020. Participants are randomly assigned to an intervention or control group in randomized controlled trial research. While patients in the control group often get a placebo therapy or procedure, those in the interventional group receive the treatment being studied. We found three studies eligible to include in the review. One study evaluated 73 individuals who received general anesthesia for dental treatment. There were 72 and 84 individuals in the second and third investigations, respectively. All the participants of the three studies were divided randomly into two groups and were subjected to dexmedetomidine and midazolam as sedative agents. We gave the evidence an "extremely low certainty" rating. Because there are just three short trials with unusual parameters for comparison, the results are questionable. Overall, the results do not allow us to draw any firm conclusions. Three randomized controlled trials included in this systematic review reported data with varying conclusions; hence we recommend more randomized controlled trials to be conducted on this subject matter.
PubMed: 36176880
DOI: 10.7759/cureus.28452 -
Journal of the Indian Society of... 2021Pain, fear, and anxiety have long been associated with pediatric dentistry. A child's cooperation with a dental.procedure.usually requires various behavioral management... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pain, fear, and anxiety have long been associated with pediatric dentistry. A child's cooperation with a dental.procedure.usually requires various behavioral management strategies conveyed by the entire dental team. The use of sedatives in dental clinics for providing analgesia and anxiolysis allows the patient to respond appropriately to verbal commands and light tactile stimulation., thus making dental treatment more patient friendly and effective.
AIM
The aim of this study was to compare the safety and efficacy of dexmedetomidine versus midazolam for the management of pediatric patients in the dental clinic.
MATERIALS AND METHODS
This systematic review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six articles were selected for this systematic review. Of them, only in four articles, homogeneous data were available which were subjected to meta-analysis.
RESULTS
When compared with midazolam, premedication with dexmedetomidine resulted in much lower incidence of emergence delirium (odds ratio = 0.07, 95% confidence interval: 0.01-0.54, P = 0.01). No significant difference was observed with respect to satisfactory behavior of the child, successful parental separation, and satisfactory mask acceptance following sedation.
CONCLUSION
Both dexmedetomidine and midazolam are equally effective for the management of pediatric patients in the dental clinic. In addition, dexmedetomidine premedication is associated with lower incidence of emergence delirium and has a better margin of safety.
Topics: Child; Dexmedetomidine; Humans; Hypnotics and Sedatives; Midazolam; Premedication
PubMed: 34810337
DOI: 10.4103/jisppd.jisppd_517_20 -
CJEM Jun 2023The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children.
STUDY DESIGN
We included trials of NO in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting NO or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.
RESULTS
We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% NO (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I = 0%) and 50% NO plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I = 43%) were superior to EMLA. 50% NO was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I = 15%). For distress and pain during laceration repair, NO was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), NO was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), NO was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), NO was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), NO plus EMLA was "favorable" versus NO and EMLA alone. Common adverse effects of NO included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with NO alone (278/1147 (24.2%)) versus NO plus midazolam (48/52 (92.3%)) and NO plus fentanyl (123/201 (61.2%)).
CONCLUSIONS
There is sufficient evidence to recommend NO plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.
Topics: Child; Adolescent; Humans; Nitrous Oxide; Midazolam; Ketamine; Lacerations; Pain; Anesthetics, Local; Lidocaine, Prilocaine Drug Combination; Oxygen
PubMed: 37171705
DOI: 10.1007/s43678-023-00507-0 -
Medicine Oct 2020Dexmedetomidine and midazolam have become important approaches for the sedation of dental surgery. However, the comparison of these 2 drugs for the sedation of dental... (Comparative Study)
Comparative Study Meta-Analysis
INTRODUCTION
Dexmedetomidine and midazolam have become important approaches for the sedation of dental surgery. However, the comparison of these 2 drugs for the sedation of dental surgery has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of dexmedetomidine versus midazolam for dental surgery.
METHODS
PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of dexmedetomidine versus midazolam on dental surgery are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model.
RESULTS
Five RCTs and 420 patients are included in the meta-analysis. Compared with midazolam intervention for dental surgery, dexmedetomidine intervention has similar lowest SpO2, lowest heart rate and lowest systolic blood pressure, duration of surgery, and total volume of local anesthetic, but is associated with stable and reduced lowest diastolic blood pressure.
CONCLUSIONS
Similar benefits of dexmedetomidine and midazolam intervention are observed for the sedation of dental surgery in terms of SpO2, heart rate, systolic blood pressure, and the volume of local anesthetic, but dexmedetomidine may result in more stable diastolic blood pressure.
Topics: Anesthetics, Local; Blood Pressure; Dexmedetomidine; Diastole; Heart Rate; Humans; Hypnotics and Sedatives; Midazolam; Operative Time; Oral Surgical Procedures; Oxygen; Systole
PubMed: 33120732
DOI: 10.1097/MD.0000000000022288 -
British Journal of Clinical Pharmacology Oct 2017Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review... (Meta-Analysis)
Meta-Analysis Review
AIMS
Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant.
METHODS
We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant. The clinical significance of each reported pharmacokinetic drug interaction was evaluated based on the United States Food and Drug Administration guidance document on conducting drug interaction studies. The probability of an adverse event reported in case reports being due to a drug interaction with aprepitant/fosaprepitant was determined using the Drug Interaction Probability Scale.
RESULTS
A total of 4377 publications were identified. Of these, 64 met inclusion eligibility criteria: 34 described pharmacokinetic drug interactions and 30 described adverse events ascribed to a drug interaction. Clinically significant pharmacokinetic interactions between aprepitant/fosaprepitant and bosutinib PO, cabazitaxel IV, cyclophosphamide IV, dexamethasone PO, methylprednisolone IV, midazolam PO/IV, oxycodone PO and tolbutamide PO were identified, as were adverse events resulting from an interaction between aprepitant/fosaprepitant and alcohol, anthracyclines, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin.
CONCLUSIONS
The potential for a drug interaction with aprepitant and fosaprepitant should be considered when selecting antiemetic therapy.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Ethanol; Humans; Injection Site Reaction; Morpholines; Nausea; Oxycodone; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Vomiting
PubMed: 28470980
DOI: 10.1111/bcp.13322 -
PloS One 2023The use of dexmedetomidine rather than midazolam may improve ICU outcomes. We summarized the available recent evidence to further verify this conclusion. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of dexmedetomidine rather than midazolam may improve ICU outcomes. We summarized the available recent evidence to further verify this conclusion.
METHODS
An electronic search of PubMed, Medline, Embase, Cochrane Library, and Web of Science was conducted. Risk ratios (RR) were used for binary categorical variables, and for continuous variables, weighted mean differences (WMD) were calculated, the effect sizes are expressed as 95% confidence intervals (CI), and trial sequential analysis was performed.
RESULTS
16 randomized controlled trials were enrolled 2035 patients in the study. Dexmedetomidine as opposed to midazolam achieved a shorter length of stay in ICU (MD = -2.25, 95%CI = -2.94, -1.57, p<0.0001), lower risk of delirium (RR = 0.63, 95%CI = 0.50, 0.81, p = 0.0002), and shorter duration of mechanical ventilation (MD = -0.83, 95%CI = -1.24, -0.43, p<0.0001). The association between dexmedetomidine and bradycardia was also found to be significant (RR 2.21, 95%CI 1.31, 3.73, p = 0.003). We found no difference in hypotension (RR = 1.44, 95%CI = 0.87, 2.38, P = 0.16), mortality (RR = 1.02, 95%CI = 0.83, 1.25, P = 0.87), neither in terms of adverse effects requiring intervention, hospital length of stay, or sedation effects.
CONCLUSIONS
Combined with recent evidence, compared with midazolam, dexmedetomidine decreased the risk of delirium, mechanical ventilation, length of stay in the ICU, as well as reduced patient costs. But dexmedetomidine could not reduce mortality and increased the risk of bradycardia.
Topics: Humans; Midazolam; Dexmedetomidine; Respiration, Artificial; Bradycardia; Intensive Care Units; Hypnotics and Sedatives; Delirium
PubMed: 37963140
DOI: 10.1371/journal.pone.0294292