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The Cochrane Database of Systematic... Oct 2018Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal models of cerebrovascular disease. However, the sedative effects of GABA receptor agonists have limited their wider application in people with acute stroke, due to the potential risk of stupor. This is an update of a Cochrane Review first published in 2013, and previously updated in 2014 and 2016.
OBJECTIVES
To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (accessed May 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) 2018, Issue 4 (accessed May 2018), MEDLINE (from 1949 to May 2018), Embase (from 1980 to May 2018), CINAHL (from 1982 to May 2018), AMED (from 1985 to May 2018), and 11 Chinese databases (accessed May 2018). In an effort to identify further published, unpublished, and ongoing trials we searched ongoing trial registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating GABA receptor agonists versus placebo for people with acute stroke (within 12 hours after stroke onset), with the primary outcomes of efficacy and safety.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed the risk of bias. We used the GRADE approach to assess the quality of the evidence.
MAIN RESULTS
We included five trials with 3838 participants (acute ischemic or hemorrhagic stroke patients, 3758 analyzed). Most of the participants recruited had acute ischaemic stroke, with limited data available from participants with other stroke subtypes, including total anterior circulation syndrome (TACS). The methodological quality of the included trials was generally good, with an unclear risk for selection bias only. For death and dependency at three months, pooled results did not find a significant difference for chlormethiazole versus placebo (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.96 to 1.11; four trials; 2909 participants; moderate-quality evidence) and for diazepam versus placebo (RR 0.94, 95% CI 0.82 to 1.07; one trial; 849 participants; moderate-quality evidence). The most frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; 2527 participants; moderate-quality evidence) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46; two trials; 2527 participants; moderate-quality evidence).
AUTHORS' CONCLUSIONS
This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke. More well-designed RCTs with large samples of participants with total anterior circulation syndrome are required to determine if there are benefits for this subgroup. Somnolence and rhinitis are frequent adverse events related to chlormethiazole.
Topics: Acute Disease; Chlormethiazole; Diazepam; Disorders of Excessive Somnolence; GABA Agonists; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic; Rhinitis; Stroke; gamma-Aminobutyric Acid
PubMed: 30376593
DOI: 10.1002/14651858.CD009622.pub5 -
Diving and Hyperbaric Medicine Jun 2019Physiological changes are induced by immersion, swimming and using diving equipment. Divers must be fit to dive. Using medication may impact the capacity to adapt to...
BACKGROUND
Physiological changes are induced by immersion, swimming and using diving equipment. Divers must be fit to dive. Using medication may impact the capacity to adapt to hyperbaric conditions. The aim of this systematic review is to assess the interaction of diving/hyperbaric conditions and medication and to provide basic heuristics to support decision making regarding fitness to dive in medicated divers.
METHODS
This was a systematic review of human and animal studies of medications in the hyperbaric environment. Studies were subdivided into those describing a medication/hyperbaric environment interaction and those concerned with prevention of diving disorders. Studies without a relation to diving with compressed air, and those concerning oxygen toxicity, hyperbaric oxygen therapy or the treatment of decompression sickness were excluded.
RESULTS
Forty-four studies matched the inclusion criteria. Animal studies revealed that diazepam and valproate gave limited protection against the onset of the high-pressure neurological syndrome. Lithium had a protective effect against nitrogen-narcosis and losartan reduced cardiac changes in repetitive diving. Human studies showed no beneficial or dangerous pressure-related interactions. In prevention of diving disorders, pseudoephedrine reduced otic barotrauma, vitamins C and E reduced endothelial dysfunction after bounce diving and hepatic oxidative stress in saturation diving.
DISCUSSION AND CONCLUSIONS
Animal studies revealed that psycho-pharmaceuticals can limit the onset of neurologic symptoms and cardiovascular protective drugs might add a potential protective effect against decompression sickness. No evidence of significant risks due to changes in pharmacologic mechanisms were revealed and most medication is not a contraindication to diving. For improving decision making in prescribing medicine for recreational and occupational divers and to enhance safety by increasing our understanding of pharmacology in hyperbaric conditions, future research should focus on controlled human studies.
Topics: Animals; Decompression Sickness; Diving; Humans; Hyperbaric Oxygenation; Inert Gas Narcosis; Swimming
PubMed: 31177519
DOI: 10.28920/dhm49.2.127-136 -
Indian Journal of Psychiatry 2017Published studies have not demonstrated the benefits of the practice of psychotropic PRN administration.
BACKGROUND
Published studies have not demonstrated the benefits of the practice of psychotropic PRN administration.
AIM
The goal of this study is to perform a systematic review on pro re nata (PRN) psychotropic medications administration in children and adolescents and examine the safety and effectiveness of this practice in child and adolescent psychiatric care units.
SETTINGS AND DESIGN
This is a systematic review.
MATERIALS AND METHODS
Several databases were searched till date. One hundred and sixty-five titles and abstracts were found and a total of 14 studies, for which most were retrospective, met the absolute criteria. The patients studied were children, adolescents and patients that presented to the emergency room or admitted as inpatient.
RESULTS
Indications for admission included aggression and agitation for all the studies. Most the medications used include haloperidol, olanzapine, diazepam, and risperidone. Commonly reported adverse effects following the administration of the PRN medications were sleepiness, acute dystonia, and drowsiness. The effectiveness of PRN medications, which was reported in four of reviewed studies, ranged from 30% to 50%.
CONCLUSION
Different effectiveness/outcome measures were used for all the studies; therefore, we could not generalize effectiveness across all the studies. Findings of the reviewed articles show the imperativeness of more research to evaluate the safety and effectiveness of PRN medications among child and adolescent populations.
PubMed: 29085084
DOI: 10.4103/psychiatry.IndianJPsychiatry_34_17 -
Epilepsy & Behavior : E&B Nov 2016Some guidelines or expert consensus indicate that intravenous (IV) lorazepam (LZP) is preferable to IV diazepam (DZP) for initial treatment of convulsive status... (Meta-Analysis)
Meta-Analysis Review
Is intravenous lorazepam really more effective and safe than intravenous diazepam as first-line treatment for convulsive status epilepticus? A systematic review with meta-analysis of randomized controlled trials.
BACKGROUND
Some guidelines or expert consensus indicate that intravenous (IV) lorazepam (LZP) is preferable to IV diazepam (DZP) for initial treatment of convulsive status epilepticus (SE). We aimed to critically assess all the available data on efficacy and tolerability of IV LZP compared with IV DZP as first-line treatment of convulsive SE.
METHODS
Systematic search of the literature (MEDLINE, CENTRAL, EMBASE, ClinicalTrials.gov) to identify randomized controlled trials (RCTs) comparing IV LZP versus IV DZP used as first-line treatment for convulsive SE (generalized or focal). Inverse variance, Mantel-Haenszel meta-analysis to obtain risk ratio (RR) with 95% confidence intervals (CI) of following outcomes: seizure cessation after drug administration; continuation of SE requiring a different drug; seizure cessation after a single dose of medication; need for ventilator support; clinically relevant hypotension.
RESULTS
Five RCTs were included, with a total of 656 patients, 320 randomly allocated to IV LZP and 336 to IV DZP. No statistically significant differences were found between IV LZP and IV DZP for clinical seizure cessation (RR 1.09; 95% CI 1.00 to 1.20), continuation of SE requiring a different drug (RR 0.76; 95% CI 0.57 to 1.02), seizure cessation after a single dose of medication (RR 0.96; 95% CI 0.85 to 1.08), need for ventilator support RR 0.93; 95% CI 0.61 to 1.43, and clinically relevant hypotension.
CONCLUSION
Despite its favorable pharmacokinetic profile, a systematic appraisal of the literature does not provide evidence to strongly support the preferential use of IV LZP as first-line treatment of convulsive SE over IV DZP.
Topics: Administration, Intravenous; Anticonvulsants; Diazepam; Humans; Lorazepam; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus; Treatment Outcome
PubMed: 27732915
DOI: 10.1016/j.yebeh.2016.09.020 -
Archives of Gerontology and Geriatrics 2017The present study aims to systematically review all potentially inappropriate medications for older persons included in prescribing criteria published in the last decade. (Review)
Review
OBJECTIVE
The present study aims to systematically review all potentially inappropriate medications for older persons included in prescribing criteria published in the last decade.
METHODS
A systematic review of published studies was performed. Articles describing the development of criteria for PIM Use in Older Adults published in the last decade and which provided a list of medications that should be considered inappropriate were included. The searches were conducted on Pubmed/Medline for articles published from 1st of January 2006 to 31st of December 2015. We analyzed the medications/classes reported in all criteria, most common classes and how many indications each medication made.
RESULTS
From 778 articles, 14 articles were included in our analysis (containing 14 different criteria). Europe was responsible for 8 criteria (57.2% of total) followed by Asia (3 criteria) and USA (2 criteria). More than 85% used a Delphi method. There were 729 different medications/classes reported in all criteria. Diazepam was included in all 14 criteria followed by amitriptyline (13 criteria) and doxepin (12 criteria). We found benzodiazepines, NSAIDs, antihistamines and antipsychotics were the most common drugs reported as potentially inappropriate for older persons.
CONCLUSION
The present study systematically compiled all medications included in 14 different criteria published last decade. Benzodiazepines, NSAIDs, antihistamines and antipsychotics were the most common drugs reported as potentially inappropriate for older persons. These results could help health professionals and panel experts to plan future criteria.
Topics: Humans; Inappropriate Prescribing; Pharmaceutical Preparations
PubMed: 27649514
DOI: 10.1016/j.archger.2016.09.003 -
Frontiers in Pharmacology 2020Midazolam is recommended by health guidelines for sedation and hypnosis in children. Oral solution is a suitable dosage form for children. But there is no conclusive...
Midazolam is recommended by health guidelines for sedation and hypnosis in children. Oral solution is a suitable dosage form for children. But there is no conclusive evidence for sedative-hypnosis and antianxiety effects by midazolam oral solution in children. Relevant studies were identified through searching PubMed, Embase, Cochrane Library, CINAHL, International Pharmaceuticals, four Chinese electronic databases, and relevant lists. Two reviewers independently selected trials, assessed trial quality, and extracted the data. Eighty-nine randomized controlled trials (RCTs) comparing midazolam oral solution with placebo or blank ( = 33), dexmedetomidine ( = 15), ketamine ( = 11), different midazolam doses ( = 10), midazolam injection ( = 8), chloral hydrate ( = 7), diazepam ( = 5), NO ( = 5), triclofos ( = 4), butorphanol ( = 2), fentanyl ( = 2), hydroxyzine ( = 1), and thiopental ( = 1) were identified. Meta-analysis showed no significant difference in the success rate and duration of sedation and hypnosis between midazolam oral and injectable solution ( > 0.05). The success rate of sedation and hypnosis of midazolam was higher than that of ketamine [risk ratio (RR) = 1.32, 95% CI (1.07, 1.62), = 0%, < 0.01]. No significant difference was found in the success rate of sedation and hypnosis, mask acceptance, and parental separation between midazolam oral solution and dexmedetomidine ( > 0.05), and the result of one cohort study was consistent. The results of RCTs and a prospective cohort study showed that the incidence of adverse drug reactions (ADR) was 19.57% (189/966). Incidence of adverse reactions between dose groups of (0.25, 0.5] and (0.5, 1.0] mg/kg was similar [Pf (95% CI) = 0.10 (0.04, 0.24) and Pf (95% CI) = 0.09 (0.02, 0.39), respectively], higher than that of the dose group of (0, 0.25] mg/kg [Pf (95% CI) = 0.01 (0.00, 0.19)]. Available evidence suggests that midazolam oral solution is as good as midazolam injection and dexmedetomidine and is better than ketamine. Based on efficacy and safety results, an oral midazolam solution dose of 0.5-1 mg/kg is recommended for children.
PubMed: 32256348
DOI: 10.3389/fphar.2020.00225 -
Frontiers in Psychiatry 2023Postictal agitation (PIA) after electroconvulsive therapy (ECT) is a serious clinical problem estimated to occur in 7-36% of patients and recur in 19-54% of patients....
BACKGROUND
Postictal agitation (PIA) after electroconvulsive therapy (ECT) is a serious clinical problem estimated to occur in 7-36% of patients and recur in 19-54% of patients. PIA has the potential to cause dangerous situations for the patient and staff members aside from the financial impact. To date, it is unclear which pharmacological interventions should be used in the management of PIA. This study aimed to systematically review the (preventative) pharmacological treatment options for PIA after ECT.
METHOD
A systematic search was done in PubMed, EMBASE, PsycINFO, and Web of Science from inception until 10 November 2022. We included randomized trials with any pharmacological intervention or comparison and a predefined outcome measure on PIA. Studies that solely included patients with neurodegenerative disorders or stroke were excluded. Data quality was assessed with the RoB2 and GRADE. Meta-analysis was performed if possible. This study was registered on PROSPERO under CRD42021262323.
RESULTS
We screened 2,204 articles and included 14 studies. Dexmedetomidine was investigated in 10 studies. Alfentanil, lignocaine, esmolol, midazolam, propofol, ketamine, haloperidol, and diazepam were each studied in only one study. Meta-analysis revealed an OR of 0.45 (0.32-0.63), a moderate effect size, in favor of dexmedetomidine than placebo to prevent PIA with very low heterogeneity (I = 0%). The certainty of the evidence was moderate. The other interventions studied were all found to have low certainty of evidence.
CONCLUSION
For clinical practice, we believe that our results indicate that dexmedetomidine should be considered for the prevention of PIA in patients that have previously experienced PIA.
PubMed: 37151968
DOI: 10.3389/fpsyt.2023.1170931 -
Journal of Neurology Jul 2022Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for... (Review)
Review
BACKGROUND
Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital.
METHODS
We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched.
RESULTS
Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups.
CONCLUSIONS
Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered.
Topics: Adult; Anticonvulsants; Diazepam; Humans; Lorazepam; Midazolam; Seizures; Status Epilepticus
PubMed: 35094154
DOI: 10.1007/s00415-022-10979-2 -
PloS One 2015To assess the efficacy of midazolam for anxiety control in third molar extraction surgery. (Review)
Review
PURPOSE
To assess the efficacy of midazolam for anxiety control in third molar extraction surgery.
METHODS
Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team.
RESULTS
Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone.
CONCLUSION
It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient's respiratory function must be monitored closely, because multidrug sedation is also more risky.
Topics: Anti-Anxiety Agents; Anxiety; Clinical Trials as Topic; Female; Humans; MEDLINE; Male; Midazolam; Molar; Tooth Extraction
PubMed: 25849859
DOI: 10.1371/journal.pone.0121410 -
The Cochrane Database of Systematic... May 2022Developments in ultrasound assessment of pregnancy has resulted in the increasing diagnosis of antenatal fetal issues. Many structural fetal conditions as well as... (Review)
Review
BACKGROUND
Developments in ultrasound assessment of pregnancy has resulted in the increasing diagnosis of antenatal fetal issues. Many structural fetal conditions as well as complications associated with multiple pregnancies have the potential for in-utero treatment to improve both pregnancy and neonatal outcomes. Procedures such as laser ablation for twin-twin syndrome or cord occlusion for selective fetal termination require fetal immobilisation. Immobilisation of the fetus can occur through administration of medication to the mother or directly to the fetus. This improves procedural success and reduces the ongoing risk to the pregnancy. Evidence regarding the best medication and mode of delivery helps to ensure the optimal decision is made for both the mother and the fetus.
OBJECTIVES
To assess the effects of perioperative pharmacological interventions for fetal immobilisation during fetal surgery and invasive procedures on fetal, neonatal, and maternal outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 May 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) which compared different classes of medication administered to the mother or fetus to allow in-utero procedures to be performed. We also included cluster-randomised trials but excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
We used the standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy.
MAIN RESULTS
One study with three trial reports met the inclusion criteria. This involved 54 women with a multiple pregnancy. The study was conducted in a tertiary European hospital maternal-fetal medicine unit and compared remifentanil to diazepam for fetal immobilisation and maternal sedation during fetoscopic surgery. Low-certainty evidence suggested that remifentanil may reduce fetal movement more than diazepam for two outcomes of fetal movement, one of fetal immobilisation at 40 minutes using a visual analogue score (VAS) (where 0 = immobile and 100 = baseline mobility), and one of gross body and limb movements (score was absolute number of movements), both assessed by a sonographer evaluating a taped ultrasound sequence (mean difference (MD) -65.00, 95% confidence interval (CI) -69.38 to -60.62 and MD -10.00, 95% CI -11.62 to -8.38; 1 study, 50 women). Surgeons may also report being more satisfied with the procedure when using remifentanil rather than diazepam (risk ratio (RR) 2.88, 95% CI 1.60 to 5.15; 1 study, 50 women; low-certainty evidence). However, maternal respiratory rate may decrease more during the surgical procedure with remifentanil compared with diazepam (MD -6.00, 95% CI -8.29 to -3.71; 1 study, 50 women; low-certainty evidence). Maternal sedation may also be worse with remifentanil compared with diazepam (RR 0.09, 95% CI 0.01 to 0.65; 1 study, 50 women; low-certainty evidence) measured using an observer assessment of alertness/sedation (where a score of < 4 equates to profound sedation and > 4 equates to insufficient sedation). Perinatal mortality and time taken to perform the procedure were not reported in the trial. We prespecified 20 outcomes and planned to use GRADE for 6 of them, all other outcomes were not able to be reported against for the purpose of meta-analysis due to data not being provided or unable to be interpreted. We assessed the included study at low risk of selection bias (appropriate random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (outcome assessors were blinded), attrition bias (incomplete outcome data minimal), and reporting bias. Our GRADE assessment for certainty of the evidence indicates that there is low certainty of the evidence.
AUTHORS' CONCLUSIONS
We were only able to include one study with a small number of women, from a single centre, a European tertiary hospital. This study was published in 2005 with an abstract of this trial published in 2004. This study evaluated two intravenous medications administered to the mother - remifentanil and diazepam. This study reported our prespecified primary outcome but only evaluated several of our secondary outcomes, which limited further assessment. Low-certainty evidence suggested that remifentanil may be better at reducing fetal movements and surgeons were more satisfied with the procedure. However, maternal sedation and depression of breathing may be worse with remifentanil. Further high-quality RCTs assessing both fetal and maternal medications are required to evaluate their efficacy for fetal immobilisation as well as safety for both mother and fetus.
Topics: Diazepam; Female; Fetus; Humans; Infant, Newborn; Perinatal Mortality; Pregnancy; Prenatal Care; Remifentanil
PubMed: 35553414
DOI: 10.1002/14651858.CD011068.pub2