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Annals of Palliative Medicine Aug 2021In order to increase the sample size and improve the test efficiency from a statistical perspective, we conducted a combined analysis of multiple results from similar... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In order to increase the sample size and improve the test efficiency from a statistical perspective, we conducted a combined analysis of multiple results from similar studies. In this study, we conducted a meta-analysis to investigate the sedative effect of dexmedetomidine on patients after cardiac surgery, so as to provide theoretical basis and help for clinical treatment of cardiac diseases.
METHODS
The Boolean logic search method was employed to search online databases for publications, with "dexmedetomidine", "cardiac surgery", "competitive antagonist", and "analgesic sedation" used as keywords. In addition, the literature was screened for comparative studies on the use of midazolam and propofol as controls. The Newcastle-Ottawa Scale (NOS) of Cochrane Collaborative Network was used to evaluate the pathological control studies in Meta-analysis, and the star rating system (out of 9 stars) was used to measure the results from the subjects, cases and groups. Finally, a meta-analysis was performed with Review Manager software (Cochrane).
RESULTS
Thirteen references containing mostly low-risk biases (medium-high quality) were included in this study. The meta-analysis showed no statistically obvious heterogeneity in the mechanical ventilation time (MVT) between patients in the control group (group A) or patients in the experimental group (group B) (Chi2=74.71; I2=92%; P<0.00001), showing no statistical significance (Z=1.57; P=0.12). Heterogeneity was found as a complication in both groups (Chi2=14.82; I2=60%; P=0.02), but fewer complications were observed in group B (Z=2.06, P=0.04). The sedative effect displayed by patients from the 2 groups during the induction of anesthesia was statistically heterogeneous (Chi2=6.45; I2=38%; P=0.17), but the sedative effect in group B was shown to be greater (Z=3.31, P=0.0009).
CONCLUSIONS
Dexmedetomidine can significantly reduce the mechanical ventilation time and the incidence of complications in patients after cardiac surgery, and has a high safety and good sedative effect on patients.
Topics: Cardiac Surgical Procedures; Dexmedetomidine; Humans; Hypnotics and Sedatives; Midazolam; Propofol
PubMed: 34488382
DOI: 10.21037/apm-21-1850 -
Clinical Pharmacokinetics Dec 2021Cytochromes P450 (CYP) are the major enzymes involved in hepatic metabolism of drugs. Personalization of treatment in pediatrics is a major challenge, as it must not...
BACKGROUND AND OBJECTIVE
Cytochromes P450 (CYP) are the major enzymes involved in hepatic metabolism of drugs. Personalization of treatment in pediatrics is a major challenge, as it must not only take into account genetic, environmental, and physiological factors but also ontogeny. Published data in adults show that inflammation had an isoform-specific impact on CYP activities and we aimed to evaluate this impact in the pediatric population.
METHODS
Articles listed in PubMed through 7 January, 2021 that studied the impact of inflammation on CYP activities in pediatrics were included in this systematic review. Sources of inflammation, victim drugs (CYP involved), effect of drug-disease interactions, number and age of subjects, and study design were extracted.
RESULTS
Twenty-seven studies and case reports were included. The impact of inflammation on CYP activities appeared to be age dependent and isoform-specific, with some drug-disease interactions having significant pharmacokinetic and clinical impact. For example, midazolam clearance decreases by 70%, while immunosuppressant and theophylline concentrations increase three-fold and two-fold with intensive care unit admission and infection. Cytochrome P450 activity appears to return to baseline level when the disease is resolved.
CONCLUSIONS
Studies that have assessed the impact of inflammation on CYP activity are lacking in pediatrics, yet it is a major factor to consider to improve drug efficacy or safety. The scarce current data show that the impact of inflammation is isoform and age dependent. An effort must be made to improve the understanding of the impact of inflammation on CYP activities in children to better individualize treatment.
Topics: Adult; Child; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Inflammation; Midazolam; Pediatrics
PubMed: 34462878
DOI: 10.1007/s40262-021-01064-4 -
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 -
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 -
Frontiers in Medicine 2021Remimazolam is a new ultrashort-acting benzodiazepine. Remimazolam has been approved for procedural sedation by the US Food and Drug Administration in 2020. However,...
Remimazolam is a new ultrashort-acting benzodiazepine. Remimazolam has been approved for procedural sedation by the US Food and Drug Administration in 2020. However, prior trials and the participants they enrolled were limited. In this meta-analysis, we investigated the effectiveness and adverse events (AEs) of remimazolam during procedural sedation. The study protocol was registered (doi: 10.37766/inplasy2020.8.0043), and six databases were searched. We performed meta-analysis, trial sequential analysis (TSA), and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for judging the certainty of evidence (CoE). A total of five randomized controlled trials with 1,248 participants were included. Compared with the use of midazolam, the utilization of remimazolam resulted in an increase in procedure success rate [odds ratio (OR) = 9.01, 95% confidence interval (CI): 2.35-34.57], a reduction in the application of rescue medication (OR = 13.58, 95% CI: 3.46-53.28), a decrease in time to recovery [minutes, weighted mean difference (WMD) = -5.70, 95% CI: -8.68 to -2.72], and a better cognitive recovery of Hopkins Verbal Learning Test-Revised (WMD = 5.22, 95% CI: 2.88-7.55). No difference was found in completion of procedure (OR = 1.68, 95% CI: 0.72-3.90) with inconclusive in TSA. Despite no difference of total AEs (OR = 0.60, 95% CI: 0.24-1.50), more detailed analysis of AEs remained inconclusive in TSA. The GRADE assessment demonstrated low to very low CoE. Our analysis suggested that remimazolam may be a better choice for procedural sedation than midazolam. Nevertheless, further studies are warranted to conclusively establish its safety.
PubMed: 34386505
DOI: 10.3389/fmed.2021.641866 -
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 -
Contemporary Clinical Dentistry 2021The aim of this study was to systematically identify and evaluate the available literature on the effectiveness of intranasal midazolam sedation compared with midazolam... (Review)
Review
AIM
The aim of this study was to systematically identify and evaluate the available literature on the effectiveness of intranasal midazolam sedation compared with midazolam administered through other routes in the sedation and behavior management of children during dental treatment.
MATERIALS AND METHODS
The search was done using electronic databases such as PubMed Central, Cochrane Database of Systematic Reviews, LILACS, ScienceDirect, and SIGLE. All studies comparing the sedative effect and behavior management effectiveness of intranasal midazolam with midazolam administered through other routes in children were included.
RESULTS
Electronic database search identified 163 articles, out of which 143 were excluded after reading titles and removing duplication. The remaining 20 studies were evaluated in detail. A final of 13 studies were included based on the inclusion criteria. Among the 13 studies included in the present review, a high risk of bias was noted in all the 13 articles. There was no adequate blinding of personnel and participants in the study, allocation concealment was improper and presence of inadequate blinding of the outcome assessment. . Statistically, no significant difference was observed between intranasal midazolam and other midazolam routes on behavior and sedation level in the studies included in this review.
CONCLUSION
Limited studies are available pertaining to the sedative and behavioral effects of intranasal midazolam, and thus, this review recommends need for more research evaluating the sedative effect of intranasal midazolam in comparison with midazolam administered through other routes in the behavior management of children during dental treatment.
PubMed: 34220149
DOI: 10.4103/ccd.ccd_470_20 -
PloS One 2021Urodynamic studies in rats and mice are broadly used to examine pathomechnisms of disease and identify and test therapeutic targets. This review aims to highlight the...
Urodynamic studies in rats and mice are broadly used to examine pathomechnisms of disease and identify and test therapeutic targets. This review aims to highlight the effects of the anesthetics on the lower urinary tract function and seeks to identify protocols that allow recovery from anesthesia and repeated measurements while preserving the function which is being studied. All studies published in English language, which compared the data obtained under various types of anesthesia and the urodynamics performed in awake animals were included. It appears that urethane, an anesthetic recommended extensively for the investigation of lower urinary tract function, is appropriate for acute urodynamic studies only. Major advantages of urethane are its stability and ability to preserve the micturition reflex. Due to its toxicity and carcinogenicity, urethane anesthesia should not be used for recovery procedures. This review evaluated available alternatives including propofol, isoflurane and combinations of urethane, ketamine/xylazine, ketamine/medetomidine, and/or fentanyl/fluanisone/midazolam. Different effects have been demonstrated among these drugs on the urinary bladder, the urethral sphincter, as well as on their neuroregulation. The lowest incidence of adverse effects was observed with the use of a combination of ketamine and xylazine. Although the variations in the reviewed study protocols represent a limitation, we believe that this summary will help in standardizing and optimizing future experiments.
Topics: Anesthesia; Anesthetics; Animals; Mice; Rats; Reflex; Urinary Bladder; Urination; Urodynamics
PubMed: 34166394
DOI: 10.1371/journal.pone.0253192 -
BMC Pulmonary Medicine Jun 2021Patients undergoing bronchoscopy in spontaneous breathing are prone to hypoxaemia and hypercapnia. Sedation, airway obstruction, and lung diseases impair respiration and...
BACKGROUND
Patients undergoing bronchoscopy in spontaneous breathing are prone to hypoxaemia and hypercapnia. Sedation, airway obstruction, and lung diseases impair respiration and gas exchange. The restitution of normal respiration takes place in the recovery room. Nonetheless, there is no evidence on the necessary observation time. We systematically reviewed current guidelines on bronchoscopy regarding sedation, monitoring and recovery.
METHODS
This review was registered at the PROSPERO database (CRD42020197476). MEDLINE and awmf.org were double-searched for official guidelines, recommendation or consensus statements on bronchoscopy from 2010 to 2020. The PICO-process focussed on adults (Patients), bronchoscopy with maintained spontaneous breathing (Interventions), and recommendations regarding the intra- and postprocedural monitoring and sedation (O). The guideline quality was graded. A catalogue of 54 questions was answered. Strength of recommendation and evidence levels were recorded for each recommendation.
RESULTS
Six guidelines on general bronchoscopy and three expert statements on special bronchoscopic procedures were identified. Four guidelines were evidence-based. Most guidelines recommend sedation to improve the patient's tolerance. Midazolam combined with an opioid is preferred. The standard monitoring consists of non-invasive blood pressure, and pulse oximetry, furthermore electrocardiogram in cardiac patients. Only one guideline discusses hypercapnia and capnometry, but without consensus. Two guidelines discuss a recovery time of two hours, but a recommendation was not given because of lack of evidence.
CONCLUSION
Evidence for most issues is low to moderate. Lung-diseased patients are not represented by current guidelines. Capnometry and recovery time lack evidence. More primary research in these fields is needed so that future guidelines may address these issues, too.
Topics: Adult; Analgesics, Opioid; Blood Gas Monitoring, Transcutaneous; Bronchoscopy; Carbon Dioxide; Conscious Sedation; Guidelines as Topic; Humans; Hypercapnia; Midazolam; Patient Safety
PubMed: 34112130
DOI: 10.1186/s12890-021-01532-4 -
Palliative Medicine Jun 2021COVID-19 has tragically resulted in over 2.5 million deaths globally. Despite this, there is a lack of research on how to care for patients dying of COVID-19,...
BACKGROUND
COVID-19 has tragically resulted in over 2.5 million deaths globally. Despite this, there is a lack of research on how to care for patients dying of COVID-19, specifically pharmacological management of symptoms.
AIM
The aim was to determine the dose ranges of pharmacological interventions commonly used to manage symptoms in adult patients dying of COVID-19, establish how effectiveness of these interventions was measured, and whether the pharmacological interventions were effective.
DESIGN
This was a rapid systematic review with narrative synthesis of evidence, prospectively registered on PROSPERO (ID: CRD42020210892).
DATA SOURCES
We searched MEDLINE, EMBASE, CINAHL via the NICE Evidence Health Databases Advanced Search interface; medRxiv; the Cochrane COVID-19 Study Register; and Google Scholar with no date limits. We included primary studies which documented care of patients dying of COVID-19 under the care of a specialist palliative care team.
RESULTS
Seven studies, documenting the care of 493 patients met the inclusion criteria. Approximately two thirds of patients required a continuous subcutaneous infusion with median doses of 15 mg morphine and 10 mg midazolam in the last 24 h of life. Four studies described effectiveness by retrospective review of documentation. One study detailed the effectiveness of individual medications.
CONCLUSIONS
A higher proportion of patients required continuous subcutaneous infusion than is typically encountered in palliative care. Doses of medications required to manage symptoms were generally modest. There was no evidence of a standardised yet holistic approach to measure effectiveness of these medications and this needs to be urgently addressed.
Topics: Adult; COVID-19; Humans; Morphine; Palliative Care; Retrospective Studies; SARS-CoV-2
PubMed: 33983081
DOI: 10.1177/02692163211013255