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The Cochrane Database of Systematic... Nov 2022Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and... (Review)
Review
BACKGROUND
Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life.
OBJECTIVES
To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.
SEARCH METHODS
We searched CENTRAL, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial register ISRCTN in August 2021. We also checked the reference lists of relevant articles to identify additional studies.
SELECTION CRITERIA
We included randomized controlled trials (RCT), quasi-RCTs and cluster-randomized trials comparing drugs used for the management of pain or sedation, or both, during therapeutic hypothermia: any opioids (e.g. morphine, fentanyl), alpha-2 agonists (e.g. clonidine, dexmedetomidine), N-Methyl-D-aspartate (NMDA) receptor antagonist (e.g. ketamine), other analgesics (e.g. paracetamol), and sedatives (e.g. benzodiazepines such as midazolam) versus another drug, placebo, no intervention, or non-pharmacological interventions. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies identified by the search strategy for inclusion. We planned to use the GRADE approach to assess the certainty of evidence. We planned to assess the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We planned to evaluate treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. MAIN RESULTS: We did not find any completed studies for inclusion. Amongst the four excluded studies, topiramate and atropine were used in two and one trial, respectively; one study used dexmedetomidine and was initially reported in 2019 to be a randomized trial. However, it was an observational study (correction in 2021). We identified one ongoing study comparing dexmedetomidine to morphine.
AUTHORS' CONCLUSIONS
We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Clonidine; Hypothermia, Induced; Pain; Morphine Derivatives; Observational Studies as Topic
PubMed: 36354070
DOI: 10.1002/14651858.CD015023.pub2 -
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 -
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 -
Clinical Pharmacokinetics Nov 2022An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze... (Review)
Review
The Cytokine Release Syndrome and/or the Proinflammatory Cytokines as Underlying Mechanisms of Downregulation of Drug Metabolism and Drug Transport: A Systematic Review of the Clinical Pharmacokinetics of Victim Drugs of this Drug-Disease Interaction Under Different Clinical Conditions.
BACKGROUND AND OBJECTIVE
An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze the clinical studies that assessed the pharmacokinetics of victim drugs of this drug-disease interaction in the presence of different scenarios of cytokine modulation in comparison with baseline conditions.
METHODS
We conducted a systematic review by searching the PubMed-MEDLINE database from inception until February 2022 to retrieve prospective and/or retrospective observational studies, population pharmacokinetic studies, phase I studies, and/or case series/reports that investigated the impact of cytokine modulation on the pharmacokinetic behavior of victim drugs. Only studies providing quantitative pharmacokinetic data of victim drugs by comparing normal status versus clinical conditions with documented cytokine modulation or by assessing the influence of anti-inflammatory biological agents on metabolism and/or transport of victim drugs were included.
RESULTS
Overall, 26 studies were included. Rheumatoid arthritis (6/26; 23.1%) and sepsis (5/26; 19.2%) were the two most frequently investigated pro-inflammatory clinical scenarios. The victim drug most frequently assessed was midazolam (14/26; 53.8%; as a probe for cytochrome P450 [CYP] 3A4). Cytokine modulation showed a moderate inhibitory effect on CYP3A4-mediated metabolism (area under the concentration-time curve increase and/or clearance decrease between 1.98-fold and 2.59-fold) and a weak-to-moderate inhibitory effect on CYP1A2, CYP2C9, and CYP2C19-mediated metabolism (in the area under the concentration-time curve increase or clearance decrease between 1.29-fold and 1.97-fold). Anti-interleukin-6 agents showed remarkable activity in counteracting downregulation of CYP3A4-mediated activity (increase in the area under the concentration-time curve between 1.75-fold and 2.56-fold).
CONCLUSIONS
Cytokine modulation may cause moderate or weak-to-moderate downregulation of metabolism/transport of victim drugs, and this may theoretically have relevant clinical consequences.
Topics: Humans; Cytochrome P-450 CYP3A; Cytokine Release Syndrome; Cytokines; Down-Regulation; Prospective Studies; Retrospective Studies; Drug Interactions
PubMed: 36059001
DOI: 10.1007/s40262-022-01173-8 -
Cureus Jun 2022We aim to discuss the efficacy and adverse effects of using ketamine in agitated patients in the emergency department (ED) compared with the combination therapy of... (Review)
Review
A Comparative Analysis Between Ketamine Versus Combination of Midazolam and Haloperidol for Rapid Safe Control of Agitated Patients in Emergency Department: A Systematic Review.
We aim to discuss the efficacy and adverse effects of using ketamine in agitated patients in the emergency department (ED) compared with the combination therapy of haloperidol with benzodiazepine. This systematic review followed Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. An electronic search from PubMed/Medline, Cochrane library, and Google Scholar was conducted from their inception to 30 April 2022. We included agitated patients in ED who were given infusion with ketamine only. Our comparative group was patients infused with combined therapy of haloperidol and benzodiazepine. We did not include letters, case reports, abstracts, conference papers, appraisals, reviews, and studies where full text was unavailable. We did not put any language restrictions. Three studies were selected in our manuscript (one cohort and two randomized controlled trials). All three studies showed that ketamine was used to achieve sedation in less time than the other group. However, two studies reported significantly more adverse effects in ketamine-infused groups. We concluded that ketamine use is superior when its primary focus is to sedate the patient as quickly as possible, but it carries some side effects that should be considered. However, we still need more studies assessing the efficacy of ketamine in agitated patients presenting in the ED.
PubMed: 35891834
DOI: 10.7759/cureus.26162 -
Advances in Health Sciences Education :... Oct 2022Within the field of robots in medical education, most of the work done during the last years has focused on surgeon training in robotic surgery, practicing surgery... (Review)
Review
Within the field of robots in medical education, most of the work done during the last years has focused on surgeon training in robotic surgery, practicing surgery procedures through simulators. Apart from surgical education, robots have also been widely employed in assistive and rehabilitation procedures, where education has traditionally focused in the patient. Therefore, there has been extensive review bibliography in the field of medical robotics focused on surgical and rehabilitation and assistive robots, but there is a lack of survey papers that explore the potential of robotics in the education of healthcare students and professionals beyond their training in the use of the robotic system. The scope of the current review are works in which robots are used as didactic tools for the education of professionals in health sciences, investigating the enablers and barriers that affect the use of robots as learning facilitators. Systematic literature searches were conducted in WOS and Scopus, yielding a total of 3812 candidate papers. After removing duplicates, inclusion criteria were defined and applied, resulting in 171 papers. An in-depth quality assessment was then performed leading to 26 papers for qualitative synthesis. Results show that robots in health sciences education are still developed with a roboticist mindset, without clearly incorporating aspects of the teaching/learning process. However, they have proven potential to be used in health sciences as they allow to parameterize procedures, autonomously guide learners to achieve greater engagement, or enable collective learning including patients and instructors "in the loop". Although there exist documented added-value benefits, further research and efforts needs to be done to foster the inclusion of robots as didactic tools in the curricula of health sciences professionals. On the one hand, by analyzing how robotic technology should be developed to become more flexible and usable to support both teaching and learning processes in health sciences education, as final users are not necessarily well-versed in how to use it. On the other, there continues to be a need to develop effective and standard robotic enhanced learning evaluation tools, as well good quality studies that describe effective evaluation of robotic enhanced education for professionals in health sciences. As happens with other technologies when applied to the health sciences field, studies often fail to provide sufficient detail to support transferability or direct future robotic health care education programs.
Topics: Humans; Robotics; Midazolam; Health Personnel; Curriculum; Learning
PubMed: 35771316
DOI: 10.1007/s10459-022-10118-6 -
Children (Basel, Switzerland) Apr 2022The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing... (Review)
Review
OBJECTIVE
The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing of traumatic lacerations in paediatric emergency departments.
METHODOLOGY
A systematic review of clinical trials was completed in July 2021. The databases consulted were PUBMED, SCOPUS, WEB OF SCIENCE, NICE and Virtual Health Library.
ELIGIBILITY CRITERIA
randomised and nonrandomised clinical trials. Two independent, blinded reviewers performed the selection and data extraction. The participants were 746 children, of whom, 377 received intranasal midazolam. All of the children were admitted to an emergency department for traumatic lacerations that required suturing. The quality of the articles was evaluated with the Jadad scale. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
RESULTS
Nine studies were included in the review. The intranasal administration of midazolam in healthy children produces anxiolysis and minimal/moderate sedation without serious side effects. Although there are combinations of parenteral drugs that produce deeper sedation, they also have greater adverse effects. No significant differences in the initiation of sedation and the suture procedure were found between the intranasal route and the parenteral route.
CONCLUSIONS
The use of intranasal midazolam in healthy children produces sufficiently intense and long-lasting sedation to allow for the suturing of traumatic lacerations that do not present other complications; therefore, this drug can be used effectively in paediatric emergency departments.
PubMed: 35626821
DOI: 10.3390/children9050644 -
Frontiers in Medicine 2022Myoclonic movement is a very common but undesirable phenomenon during the induction of general anesthesia using etomidate. Such movement may cause unnecessary problems....
BACKGROUND
Myoclonic movement is a very common but undesirable phenomenon during the induction of general anesthesia using etomidate. Such movement may cause unnecessary problems. Currently, there is an increasing number of drugs for preventing etomidate-induced myoclonus (EM). However, direct comparisons of various drugs are lacking, and this interferes with clinical decision-making. Our network meta-analysis (NMA) aimed to compare the efficacy of different drugs for the prevention of moderate-to-severe general myoclonus.
METHODS
Using several biomedical databases, randomized controlled trials (RCTs) published in English from inception to August 22, 2021 were searched. Among the various interventions, we selected nine types of intervention drugs (dexmedetomidine, etomidate, lidocaine, NMDA receptor antagonist, κ opioid receptor agonist, μ opioid receptor agonist, muscle relaxant, gabapentin, and midazolam) for comparison, according to the number of studies. Bayesian NMA was performed using STATA16 and R softwares. The relative risk of EM was assessed using risk ratios (RRs) and the corresponding 95% confidence intervals (CI).
RESULTS
A total of 31 RCTs (3209 patients) were included. NMA results showed that, compared with a placebo, etomidate (RR 4.0, 95%CI 2.1-7.8), κ opioid receptor agonist (RR 2.9, 95%CI 1.9-4.6), μ opioid receptor agonist (RR 3.1, 95%CI 2.3-4.3), NMDA receptor antagonist (RR 1.7, 95%CI 1.0-2.8), dexmedetomidine (RR 2.4, 95%CI 1.5-3.9), lidocaine (RR 2.1, 95%CI 1.2-3.9), and midazolam (RR 2.2, 95%CI 1.5-3.2) can significantly reduce the risk of EM. In contrast, the effects of muscle relaxants (RR 2.1, 95%CI 0.81-5.3) and gabapentin (RR 2.8, 95%CI 0.92-9.3) were inconclusive. Further subgroup analyses showed that preoperative low-dose etomidate, μ-opioid receptor agonist, and κ-opioid receptor agonist were significantly better than other interventions in the prevention of moderate to severe EM.
CONCLUSION
Preoperative use of small doses of etomidate or opioids may be the most effective way to avoid EM, especially moderate and severe EM, which makes anesthesia induction safer, more stable, and aligns better with the requirements of comfortable medicine.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], [CRD4202127706].
PubMed: 35559341
DOI: 10.3389/fmed.2022.799156 -
Dental and Medical Problems 2022Demand for dental implants has increased in recent years and the use of conscious sedation for this type of surgery can be of great benefit. Therefore, the aim of this... (Meta-Analysis)
Meta-Analysis Review
Demand for dental implants has increased in recent years and the use of conscious sedation for this type of surgery can be of great benefit. Therefore, the aim of this systematic review was to evaluate the scientific literature related to the effect of conscious sedation on the reduction of anxiety, and patient and surgeon satisfaction. The Embase, PubMed, ProQuest, Scopus, Ovid, and Cochrane databases were searched without limitations. According to the inclusion and exclusion criteria determined for the study, 10 articles were selected for the final review during several screening stages. These studies were reviewed in their full-text form by the research team and the intended data was extracted. The risk of bias was assessed for each of the selected articles. Five studies were ultimately included. Two of the them compared local anesthesia and conscious sedation, while another 2 compared the consequences of different types of conscious sedation. The anxiety reduction and patient and surgeon satisfaction data was collated. Midazolam was the most frequently used agent. After a thorough review of the final articles extracted based on the study protocol, it was concluded that the use of conscious sedation during implant surgery reduces patient anxiety, and also increases the satisfaction of the patient and surgeon.
Topics: Anxiety; Conscious Sedation; Dental Implants; Humans; Patient Satisfaction; Personal Satisfaction
PubMed: 35403382
DOI: 10.17219/dmp/141868 -
Cureus Mar 2022Remimazolam is made by combining midazolam and remifentanil as an alternative to conventional sedatives. To evaluate the efficacy of remimazolam for sedation in... (Review)
Review
Efficacy of Remimazolam for Procedural Sedation in American Society of Anesthesiologists (ASA) I to IV Patients Undergoing Colonoscopy: A Systematic Review and Meta-Analysis.
Remimazolam is made by combining midazolam and remifentanil as an alternative to conventional sedatives. To evaluate the efficacy of remimazolam for sedation in patients undergoing colonoscopy, we conducted a systematic review and meta-analysis of the available randomized controlled trials (RCTs) comparing remimazolam and midazolam. A search was conducted using PubMed, Cochrane Library, and clinicaltrial.gov from inception till December 26, 2021, for RCTs that investigated the efficacy of remimazolam during the above-mentioned procedure. There was no restriction of language. A quality assessment was performed using the Cochrane Risk-of-Bias tool. The data were pooled, and a meta-analysis was completed. The systemic review was conducted in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guideline statement. Three randomized controlled trials involving 539 patients were included in the meta-analysis. Compared with midazolam during colonoscopy, remimazolam results in reduced need for top-up doses (RR= 3.45, 95% CI=1.07 to 11.14; P=0.04, I=84%). The need for rescue medication was reduced with remimazolam as compared to midazolam (RR=2.42, 95%CI=1.04 to 5.61; P=0.04, I=96%). There was no significant difference observed between the two drugs on completion of colonoscopy and the overall procedural sedation, but the sensitivity analysis favored remimazolam over midazolam for procedural sedation (RR=4.08, 95%CI=2.35 to 7.09; P<0.00001, I=39%). This analysis demonstrates the advantages of remimazolam over other agents and sets a platform for relevant future studies.
PubMed: 35399486
DOI: 10.7759/cureus.22881