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Epilepsia Oct 2023Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed... (Meta-Analysis)
Meta-Analysis
Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.
Topics: Infant, Newborn; Humans; Anticonvulsants; Levetiracetam; Phenytoin; Consensus; Epilepsy; Seizures
PubMed: 37655702
DOI: 10.1111/epi.17745 -
Frontiers in Pediatrics 2023To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis. (Review)
Review
OBJECTIVE
To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis.
METHODS
Cochrane Library, Pubmed, Embase, and Web of Science were searched from inception to July 2023. Randomized controlled trials (RCTs) of intranasal Dex vs. oral midazolam in pediatric premedication were collected. Stata 15.0 statistical software was used to analyze the collected data. Relative risk (RR) and 95% confidence interval (CI) were used as effect sizes.
RESULTS
A total of 11 studies with 824 children were included, containing 415 patients in the Dex group and 409 patients in the midazolam group. Compared with the oral midazolam group, the intranasal Dex group had a better preoperative sedation effect at parent-child separation (RR = 1.37, 95% CI: 1.14-1.64) and anesthesia induction (RR = 2.08, 95% CI: 1.03-4.22). In addition, there was no significant difference in the incidence of analgesia remedy (RR = 0.60, 95% CI: 0.36-1.00) the acceptance of anesthesia masks (RR = 0.97, 95% CI: 0.83-1.12), and incidence of adverse events between (RR = 0.25, 95% CI: 0.06-1.13, = 0.072) between the intranasal Dex and oral midazolam groups.
CONCLUSION
Compared with oral midazolam, intranasal Dex has better sedative effects of parent-child separation and anesthesia induction in pediatric premedication, but there was no difference in the incidence of anesthesia remedy, anesthesia mask acceptance, and incidence of adverse events. Therefore, compared with oral midazolam, intranasal Dex is a better choice for premedication in children.
PubMed: 38027288
DOI: 10.3389/fped.2023.1264081 -
Oral and Maxillofacial Surgery Dec 2023Pediatric dental surgeries are associated with the emotions of fear, anxiety, and other behavioral disturbances of children that need to be managed. Sedation using drugs... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis comparing the efficacy of dexmedetomidine to midazolam as premedication and a sedative agent in pediatric patients undergoing dental procedures.
INTRODUCTION
Pediatric dental surgeries are associated with the emotions of fear, anxiety, and other behavioral disturbances of children that need to be managed. Sedation using drugs like dexmedetomidine (DEX) and midazolam (MID) is a common pharmacological behavior managing technique. We conducted this meta-analysis to evaluate the efficacy of both these drugs in current literature.
METHODOLOGY
A thorough literature search was conducted on PubMed, MEDLINE, Google Scholar, and Cochrane's database for randomized studies that compared sedative efficacy of dexmedetomidine with midazolam in children of 0-15 years of age undergoing dental surgeries. Sedation in children during dental procedure, when used as a premedication, at the time of separation from parents and at the time of mask induction, onset time, duration of anesthesia, and surgery were evaluated. The mean differences (MDs), odds ratio (OR), and their 95% confidence intervals (CIs) were calculated both for continuous and dichotomous outcome data using random-effects model.
RESULTS
Seven studies met out inclusion criteria and were analyzed. Results of premedication with DEX was associated with more anxiolysis (OR=0.29, 95% CI: 0.17-0.52, p=0.0001; I=0%) and at the time of separation from parents (OR=0.36, 95% CI: 0.19-0.69, p=0.002; I=52%) in comparison to MID. No significant differences in results were seen at mask induction (OR=0.63, 95% CI: 0.34-1.18, p=0.15; I=47%) and for sedation in children during dental procedures (OR=0.52, 95% CI: 0.07-3.70, p=0.51; I=72%). Also, there were no significant differences in onset time, duration of anesthesia, and surgery between the two agents.
CONCLUSION
DEX proved to be a better premedicant than MID for pediatric patients. No significant difference in efficacy of both sedative agents was observed in children undergoing dental treatment. More clinical trials need to be conducted to see its efficacy in dental surgeries in children of standardized ages and with standard doses.
Topics: Child; Humans; Midazolam; Dexmedetomidine; Hypnotics and Sedatives; Premedication; Anesthesia, Dental
PubMed: 35759132
DOI: 10.1007/s10006-022-01087-6 -
BMC Anesthesiology Jun 2024Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation.
METHODS
The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events.
RESULTS
A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I = 30%).
CONCLUSIONS
This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.
Topics: Dexmedetomidine; Humans; Hypnotics and Sedatives; Midazolam; Child; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 38907338
DOI: 10.1186/s12871-024-02570-1 -
British Journal of Anaesthesia Mar 2024We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency... (Meta-Analysis)
Meta-Analysis Review
Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomised trials.
BACKGROUND
We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications.
METHODS
We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates.
RESULTS
We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty).
CONCLUSION
When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine.
Topics: Adult; Child; Humans; Propofol; Midazolam; Ketamine; Network Meta-Analysis; Pain; Analgesics, Opioid; Analgesia; Emergency Service, Hospital; Intensive Care Units; Conscious Sedation; Randomized Controlled Trials as Topic
PubMed: 38185564
DOI: 10.1016/j.bja.2023.11.050 -
Obesity Reviews : An Official Journal... May 2024To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. (Review)
Review
OBJECTIVES
To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements.
METHODS
Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model.
RESULTS
Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I = 67%), increased maximal concentration (MD = 6.90 μg/ml, p = 0.006, I = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters.
CONCLUSION
This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.
PubMed: 38710656
DOI: 10.1111/obr.13759 -
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 -
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 the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
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