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British Journal of Anaesthesia Jan 2023Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques.
METHODS
Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events.
RESULTS
Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99).
CONCLUSIONS
We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.
Topics: Child; Humans; Hypnotics and Sedatives; Midazolam; Dexmedetomidine; Administration, Oral; Chloral Hydrate; Administration, Intranasal; Conscious Sedation
PubMed: 36283870
DOI: 10.1016/j.bja.2022.09.007 -
Journal of Clinical Anesthesia Jun 2020Procedural sedation for non-painful pediatric examinations outside the operating room remains a challenge, this study was designed to compare the safety and... (Meta-Analysis)
Meta-Analysis Review
STUDY OBJECTIVE
Procedural sedation for non-painful pediatric examinations outside the operating room remains a challenge, this study was designed to compare the safety and effectiveness of sedation provided by dexmedetomidine versus other sedatives including chloral hydrate, midazolam, and pentobarbital for pediatric patients to complete diagnostic examinations.
DESIGN
Systematic review and meta-analysis of RCTs.
SETTING
Pediatric procedural sedation.
INTERVENTIONS
Comparison of sedation by dexmedetomidine and chloral hydrate, or pentobarbital, or midazolam for pediatric non-painful sedation.
PATIENTS
The PubMed, Embase, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched and limited the studies to those published in English through July 30, 2018.
MEASUREMENTS
Prospective randomized clinical trials (RCTs) comparing dexmedetomidine to chloral hydrate, pentobarbital, and midazolam for pediatric procedural examinations outside the operating room were included in the meta-analysis. Search terms included dexmedetomidine, precede, adrenergic alpha-2 receptor agonists, adrenergic alpha 2 agonists, adrenergic alpha-agonists, adrenergic alpha 2 receptor agonists, chloral hydrate, pentobarbital, midazolam, AND sedation.
MAIN RESULTS
A total of 1486 studies were screened and nine RCTs were identified; 1076 patients were analyzed. Sedation with dexmedetomidine provided statistically higher incidences in completing examinations with fewer episodes of desaturation than the other sedatives did (OR 2.90, 95% CI: 1.39-6.07, P = 0.005, I = 77%; OR 0.29, 95% CI: 0.15-0.57, P = 0.0004, I = 0%, respectively).
CONCLUSIONS
The meta-analysis shows that sedation by dexmedetomidine has lower incidence of respiratory depression and provides higher success rates in completing examinations than other traditional sedatives without compromising safety, indicating a prospective clinical use for procedural sedation.
Topics: Child; Chloral Hydrate; Conscious Sedation; Dexmedetomidine; Humans; Hypnotics and Sedatives; Midazolam; Randomized Controlled Trials as Topic
PubMed: 32018129
DOI: 10.1016/j.jclinane.2020.109736 -
JAMA Neurology May 2024Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing...
IMPORTANCE
Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE.
OBJECTIVE
To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
EVIDENCE REVIEW
Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study.
FINDINGS
A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering.
CONCLUSIONS AND RELEVANCE
Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.
Topics: Humans; Status Epilepticus; Anesthetics, Intravenous; Drug Resistant Epilepsy; Anticonvulsants
PubMed: 38466294
DOI: 10.1001/jamaneurol.2024.0108 -
The Cochrane Database of Systematic... Aug 2021This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure.
OBJECTIVES
To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.
SEARCH METHODS
We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.
SELECTION CRITERIA
Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS
We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence).
AUTHORS' CONCLUSIONS
The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.
Topics: Child; Chloral Hydrate; Diagnostic Techniques, Neurological; Humans; Hydroxyzine; Hypnotics and Sedatives; Midazolam; Pentobarbital
PubMed: 34397100
DOI: 10.1002/14651858.CD011786.pub3 -
Life Sciences Nov 2021To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes. (Meta-Analysis)
Meta-Analysis
AIM
To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes.
DATA SOURCE
A systematic review of the literature to find studies with isoflurane, ketamine, halothane, pentobarbital, or thiopental just before euthanasia of laboratory rats or mice.
STUDY SELECTION
Controlled studies with quantitative data available.
DATA EXTRACTION
The search, data extraction, and risk of bias (RoB) were performed independently by two reviewers using a structured form. For each outcome, an effect size (ES) was calculated relative to the control group. Meta-analysis was performed using robust variance meta-regression for hierarchical data structures, with adjustment for small samples.
DATA SYNTHESIS
We included 20 studies with 407 biological outcomes (110 unique). RoB analysis indicated that 87.5% of the domains evaluated showed unclear risk, 2% high risk, and 10.5% low risk. The effect size for all anesthetics considered together was 0.99 (CI = 0.75-1.23; p < 0.0001). Sub-analyses indicate high effect sizes for pentobarbital (1.14; CI = 0.75-1.52; p < 0.0001), and isoflurane (1.01; CI = 0.58-1.44; p = 0.0005) but not for ketamine (1.49; CI = -7.95-10.9; p = 0.295).
CONCLUSION
We showed that anesthetics interfere differently with the majority of the outcomes assessed. However, our data did not support the use of one anesthetic over others or even the killing without anesthetics. We conclude that outcomes cannot be compared among studies without considering the killing method. This protocol was registered at Prospero (CRD42019119520).
FUNDING
There was no direct funding for this research.
Topics: Anesthetics; Animals; Dose-Response Relationship, Drug; Euthanasia; Mice; Publication Bias; Rats; Risk
PubMed: 34480936
DOI: 10.1016/j.lfs.2021.119916 -
Frontiers in Pediatrics 2020We conducted this systematic review and meta-analysis to investigate the clinical effect of dexmedetomidine in preventing pediatric emergence agitation (EA) or delirium...
We conducted this systematic review and meta-analysis to investigate the clinical effect of dexmedetomidine in preventing pediatric emergence agitation (EA) or delirium (ED) following anesthesia compared with placebo or other sedatives. The databases of Pubmed, Embase, and Cochrane Library were searched until 8th January 2020. Inclusion criteria were participants with age<18 years and studies of comparison between dexmedetomidine and placebo or other sedatives. Exclusion criteria included adult studies; duplicate publications; management with dexmedetomidine alone; review or meta-analysis; basic research; article published as abstract, letter, case report, editorial, note, method, or protocol; and article presented in non-English language. Fifty-eight randomized controlled trials (RCTs) and five case-control trials (CCTs) including 7,714 patients were included. The results showed that dexmedetomidine significantly decreased the incidence of post-anesthesia EA or ED compared with placebo [OR = 0.22, 95% CI: (0.16, 0.32), = 75, < 0.00001], midazolam [OR = 0.36, 95% CI: (0.21, 0.63), = 57, = 0.0003], and opioids [OR = 0.55, 95% CI: (0.33, 0.91), = 0, = 0.02], whereas the significant difference was not exhibited compared with propofol (or pentobarbital) [OR = 0.56, 95% CI: (0.15, 2.14), = 58, = 0.39], ketamine [OR = 0.43, 95% CI: (0.19, 1.00), = 0, = 0.05], clonidine [OR = 0.54, 95% CI: (0.20, 1.45), = 0.22], chloral hydrate [OR = 0.98, 95% CI: (0.26, 3.78), = 0.98], melatonin [OR = 1.0, 95% CI: (0.13, 7.72), = 1.00], and ketofol [OR = 0.55, 95% CI: (0.16, 1.93), = 0.35]. Compared with placebo, midazolam, and opioids, dexmedetomidine significantly decreased the incidence of post-anesthesia EA or ED in pediatric patients. However, dexmedetomidine did not exhibit this superiority compared with propofol and ketamine. With regard to clonidine, chloral hydrate, melatonin, and ketofol, the results needed to be further tested due to the fact that only one trial was included for each control drug.
PubMed: 32766178
DOI: 10.3389/fped.2020.00329 -
The Canadian Journal of Neurological... Nov 2023The blood brain barrier (BBB) is a highly selective permeable barrier that separates the blood and the central nervous system. Anesthesia is an integral part of surgery,...
BACKGROUND
The blood brain barrier (BBB) is a highly selective permeable barrier that separates the blood and the central nervous system. Anesthesia is an integral part of surgery, and there is little known about the impact of anesthetics on the BBB. Therefore, it is imperative to explore reversible or modifiable variables such as anesthetic agents that influence BBB integrity. We aimed to synthesize the literature pertaining to the various effects of anesthetics on the BBB.
METHODS
MEDLINE, Embase, and Cochrane were searched from inception up to September 2022.
RESULTS
A total of 14 articles met inclusion into the review. The articles included nine randomized control studies (64.3%) and five quasi-experimental studies (35.7%). Twelve studies used volatile anesthetics, one study used fentanyl intravenously, and one study used pentobarbital or ketamine intraperitoneally. BBB structural deficits following the administration of an anesthetic agent included ultrastructural deficits, decreases in tight junctions, and decreases in BBB components. BBB functional deficits included permeability increases following exposure to volatile anesthetics. However, two studies found decreased permeability after fentanyl, pentobarbital, or ketamine exposure. Moreover, the impact of anesthetics on the BBB seems to be related to the duration of exposure. Notably, study findings also suggest that changes following anesthetic exposure demonstrate some reversibility over the short-term.
CONCLUSION
Overall, our systematic review highlights interesting findings pertaining to the impact of anesthetic agents on BBB integrity in previously healthy models. These findings and mechanisms should inspire future work to aid practitioners and healthcare teams potentially better care for patients.
PubMed: 36353901
DOI: 10.1017/cjn.2022.319